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1

Cooperative transcriptional activation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 genes by nuclear receptors including Liver-X-Receptor.  

PubMed

The ATP-binding cassette transporters ABCG5 and ABCG8 form heterodimers that limit absorption of dietary sterols in the intestine and promote cholesterol elimination from the body through hepatobiliary secretion. To identify cis-regulatory elements of the two genes, we have cloned and analyzed twenty-three evolutionary conserved region (ECR) fragments using the CMV-luciferase reporter system in HepG2 cells. Two ECRs were found to be responsive to the Liver-X-Receptor (LXR). Through elaborate deletion studies, regions containing putative LXREs were identified and the binding of LXR? was demonstrated by EMSA and ChIP assay. When the LXREs were inserted upstream of the intergenic promoter, synergistic activation by LXR?/RXR? in combination with GATA4, HNF4?, and LRH-1, which had been shown to bind to the intergenic region, was observed. In conclusion, we have identified two LXREs in ABCG5/ABCG8 genes for the first time and propose that these LXREs, especially in the ECR20, play major roles in regulating these genes. PMID:23790976

Back, Su Sun; Kim, Jinsu; Choi, Daehyung; Lee, Eui Sup; Choi, Soo Young; Han, Kyuhyung

2013-06-01

2

Expression of key genes of fatty acid oxidation, including adiponectin receptors, in skeletal muscle of Type 2 diabetic patients  

Microsoft Academic Search

Aims\\/hypothesis  Defective oxidation of long-chain fatty acids is a feature of insulin resistance and Type 2 diabetes. Our aim was to compare the expression levels of the genes encoding the major proteins and enzymes of this pathway in skeletal muscle of healthy subjects and Type 2 diabetic patients.Methods  The basal and insulin-regulated mRNA concentration of 16 genes was quantified using real-time PCR

C. Debard; M. Laville; V. Berbe; E. Loizon; C. Guillet; B. Morio-Liondore; Y. Boirie; H. Vidal

2004-01-01

3

Differential effects of sex steroid hormones on the expression of multiple first exons including a novel first exon of prolactin receptor gene in the rat liver  

Microsoft Academic Search

In addition to the known four alternative first exons E11 ,E 12 ,E 13 and E14 of the rat prolactin receptor (PRL-R) gene, a novel first exon, E15, was identified by cDNA cloning of the 58-end region of PRL-R mRNA in the rat liver. Genomic fragments containing E15 and its 58 -o r 38-flanking regions were also cloned from rat

M Tanaka; M Suzuki; T Kawana; M Segawa; M Yoshikawa; M Mori; M Kobayashi; N Nakai; T R Saito

2005-01-01

4

Estrogen receptor genes  

US Patent & Trademark Office Database

The present invention relates to an estrogen receptor gene, characterized by comprising a nucleotide sequence coding for any one of the following amino acid sequences: (a) the amino acid sequence of SEQ ID NO:1, (b) an amino acid sequence of a protein having an estrogen receptor activity, said amino acid sequence has at least 85% sequence identity with the amino acid sequence of SEQ ID NO:1, (c) an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO:2, and (d) an amino acid sequence of a protein having an estrogen receptor activity, said amino acid sequence is encoded by a nucleotide sequence having at least 85% sequence identity with a DNA having the nucleotide sequence of SEQ ID NO:2, and the like. The estrogen receptor gene and the like can be applied to assay systems for evaluating the ability of chemical substances to regulate the estrogen receptor activity.

2008-09-02

5

Multiple mechanisms induce transcriptional silencing of a subset of genes, including oestrogen receptor ?, in response to deacetylase inhibition by valproic acid and trichostatin A  

Microsoft Academic Search

Valproate (VPA) and trichostatin A (TSA), inhibitors of zinc-dependent deacetylase activity, induce reduction in the levels of mRNA encoding oestrogen receptor-? (ER?), resulting in subsequent clearance of ER? protein from breast and ovarian cell lines. Inhibition of oestrogen signalling may account for the endocrine disorders, menstrual abnormalities, osteoporosis and weight gain that occur in a proportion of women treated with

George Reid; Raphaël Métivier; Chin-Yo Lin; Stefanie Denger; David Ibberson; Tomi Ivacevic; Heike Brand; Vladimir Benes; Edison T Liu; Frank Gannon

2005-01-01

6

Taste Receptor Genes  

PubMed Central

In the past several years, tremendous progress has been achieved with the discovery and characterization of vertebrate taste receptors from the T1R and T2R families, which are involved in recognition of bitter, sweet, and umami taste stimuli. Individual differences in taste, at least in some cases, can be attributed to allelic variants of the T1R and T2R genes. Progress with understanding how T1R and T2R receptors interact with taste stimuli and with identifying their patterns of expression in taste cells sheds light on coding of taste information by the nervous system. Candidate mechanisms for detection of salts, acids, fat, complex carbohydrates, and water have also been proposed, but further studies are needed to prove their identity.

Bachmanov, Alexander A.; Beauchamp, Gary K.

2009-01-01

7

Linkage Analysis between Manic-Depressive Illness and the Region on Chromosome 15q Involved in Prader-Syndrome, including Two GABAA Receptor Subtype Genes  

Microsoft Academic Search

Cooccurrence of Prader-Willi syndrome and psychosis has been reported in a few cases. Prader-Willi syndrome is most often associated with interstitial deletion or uniparental disomy of chromosome 15qll-ql3. The cooccurrence of Prader-Willi syndrome and psychosis may thus be due to deletion of, or in the case of uniparental disomy, duplication of a gene involved in the etiology of psychosis, possibly

Henrik Ewald; Ole Mors; Tracey Flint; Torben A. Kruse

1994-01-01

8

Concordance between isolated cleft palate in mice and alterations within a region including the gene encoding the beta 3 subunit of the type A gamma-aminobutyric acid receptor.  

PubMed Central

Genetic and molecular analyses of a number of radiation-induced deletion mutations of the pink-eyed dilution (p) locus in mouse chromosome 7 have identified a specific interval on the genetic map associated with a neonatally lethal mutation that results in cleft palate. This interval, closely linked and distal to p, and bracketed by the genes encoding the alpha 5 and beta 3 subunits of the type A gamma-aminobutyric acid receptor (Gabra5 and Gabrb3, respectively), contains a gene(s) (cp1; cleft palate 1) necessary for normal palate development. The cp1 interval extends from the distal breakpoint of the prenatally lethal p83FBFo deletion to the Gabrb3 locus. Among 20 p deletions tested, there was complete concordance between alterations at the Gabrb3 transcription unit and inability to complement the cleft-palate defect. These mapping data, along with previously described in vivo and in vitro teratological effects of gamma-aminobutyric acid or its agonists on palate development, suggest the possibility that a particular type A gamma-aminobutyric acid receptor that includes the beta 3 subunit may be necessary for normal palate development. The placement of the cp1 gene within a defined segment of the larger D15S12h (p)-D15S9h-1 interval in the mouse suggests that the highly homologous region of the human genome, 15q11-q13, be evaluated for a role(s) in human fetal facial development. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4

Culiat, C T; Stubbs, L; Nicholls, R D; Montgomery, C S; Russell, L B; Johnson, D K; Rinchik, E M

1993-01-01

9

Concordance between isolated cleft palate in mice and alterations within a region including the gene encoding the [beta][sub 3] subunit of the type A [gamma]-aminobutyric acid receptor  

SciTech Connect

Genetic and molecular analyses of a number of radiation-induced deletion mutations of the pink-eyed dilution (p) locus in mouse chromosome 7 have identified a specific interval on the genetic map associated with a neonatally lethal mutation that results in cleft palate. This interval, closely linked and distal to p, and bracketed by the genes encoding the [alpha][sub 5] and [beta][sub 3] subunits of the type A [gamma]-aminobutyric acid receptor (Gabra5 and Gabrb3, respectively), contains a gene(s) (cp1; cleft palate 1) necessary for normal palate development. The cp1 interval extends from the distal breakpoint of the prenatally lethal p[sup 83FBFo] deletion to the Gabrb3 locus. Among 20 p deletions tested, there was complete concordance between alterations at the Gabrb3 transcription unit and inability to complement the cleft-palate defect. These mapping data, along with previously described in vivo and in vitro teratological effects of [gamma]-aminobutyric acid or its agonists on palate development, suggest the possibility that a particular type A [gamma]-aminobutyric acid receptor that includes the [beta][sub 3] subunit may be necessary for normal palate development. The placement of the cp1 gene within a defined segment of the larger D15S12h (p)-D15S9h-1 interval in the mouse suggests that the highly homologous region of the human genome, 15q11-q13, be evaluated for a role(s) in human fetal facial development. 29 refs., 4 figs., 1 tab.

Culiat, C.T.; Stubbs, L.; Nicholls, R.D.; Montgomery, C.S.; Russell, L.B.; Johnson, D.K. (Oak Ridge National Lab., TN (United States)); Rinchik, E.M. (Oak Ridge National Lab., TN (United States) Univ. of Florida, Gainesville (United States))

1993-06-01

10

Melatonin receptor genes in vertebrates.  

PubMed

Melatonin receptors are members of the G protein-coupled receptor (GPCR) family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A) and MT2 (or Mel1b or MTNR1B) receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C), has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor. PMID:23712359

Li, Di Yan; Smith, David Glenn; Hardeland, Rüdiger; Yang, Ming Yao; Xu, Huai Liang; Zhang, Long; Yin, Hua Dong; Zhu, Qing

2013-05-27

11

Melatonin Receptor Genes in Vertebrates  

PubMed Central

Melatonin receptors are members of the G protein-coupled receptor (GPCR) family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A) and MT2 (or Mel1b or MTNR1B) receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C), has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor.

Li, Di Yan; Smith, David Glenn; Hardeland, Rudiger; Yang, Ming Yao; Xu, Huai Liang; Zhang, Long; Yin, Hua Dong; Zhu, Qing

2013-01-01

12

Gene silencing by nuclear orphan receptors.  

PubMed

Nuclear orphan receptors represent a large and diverse subgroup in the nuclear receptor superfamily. Although putative ligands for these orphan members remain to be identified, some of these receptors possess intrinsic activating, inhibitory, or dual regulatory functions in development, differentiation, homeostasis, and reproduction. In particular, gene-silencing events elicited by chicken ovalbumin upstream promoter-transcription factors (COUP-TFs); dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX-1); germ cell nuclear factor (GCNF); short heterodimer partner (SHP); and testicular receptors 2 and 4 (TR2 and TR4) are among the best characterized. These orphan receptors are critical in controlling basal activities or hormonal responsiveness of numerous target genes. They employ multiple and distinct mechanisms to mediate target gene repression. Complex cross-talk exists between these orphan receptors at their cognate DNA binding elements and an array of steroid?nonsteroid hormone receptors, other transcriptional activators, coactivators and corepressors, histone modification enzyme complexes, and components of basal transcriptional components. Therefore, perturbation induced by these orphan receptors at multiple levels, including DNA binding activities, receptor homo- or heterodimerization, recruitment of cofactor proteins, communication with general transcriptional machinery, and changes at histone acetylation status and chromatin structures, may contribute to silencing of target gene expression in a specific promoter or cell-type context. Moreover, the findings derived from gene-targeting studies have demonstrated the significance of these orphan receptors' function in physiologic settings. Thus, COUP-TFs, DAX-1, GCNF, SHP, and TR2 and 4 are known to be required for multiple physiologic and biologic functions, including neurogenesis and development of the heart and vascular system steroidogenesis and sex determination, gametogenesis and embryonic development, and cholesterol?lipid homeostasis. PMID:15193450

Zhang, Ying; Dufau, Maria L

2004-01-01

13

The Olfactory Receptor Gene Family of Marsupials  

Microsoft Academic Search

\\u000a Olfaction in vertebrates is mediated mainly by a large family of olfactory receptors in the olfactory epithelium that belong\\u000a to the superfamily of G protein-coupled receptors. Olfactory systems are well conserved among vertebrates, including marsupials,\\u000a but there is a large variation in the numbers of olfactory genes in different animals. Most marsupials are nocturnal so depend\\u000a on their sense of

Margaret L. Delbridge; Amir Mohammadi; Jennifer A. Marshall Graves

14

The olfactory receptor gene superfamily of the mouse  

Microsoft Academic Search

Olfactory receptor (OR) genes are the largest gene superfamily in vertebrates. We have identified the mouse OR genes from the nearly complete Celera mouse genome by a comprehensive data mining strategy. We found 1,296 mouse OR genes (including ?20% pseudogenes), which can be classified into 228 families. OR genes are distributed in 27 clusters on all mouse chromosomes except 12

Xinmin Zhang; Stuart Firestein

2002-01-01

15

The androgen receptor gene mutations database.  

PubMed

The androgen receptor gene mutations database is a comprehensive listing of mutations published in journals and meetings proceedings. The majority of mutations are point mutations identified in patients with androgen insensitivity syndrome. Information is included regarding the phenotype, the nature and location of the mutations, as well as the effects of the mutations on the androgen binding activity of the receptor. The current version of the database contains 149 entries, of which 114 are unique mutations. The database is available from EMBL (NetServ@EMBL-Heidelberg.DE) or as a Macintosh Filemaker file (mc33001@musica.mcgill.ca). PMID:7937057

Patterson, M N; Hughes, I A; Gottlieb, B; Pinsky, L

1994-09-01

16

Mechanics of T cell receptor gene rearrangement  

PubMed Central

Summary The four T cell receptor genes (Tcra, Tcrb, Tcrg, Tcrd) are assembled by V(D)J recombination according to distinct programs during intrathymic T cell development. These programs depend on genetic factors, including gene segment order and recombination signal sequences. They also depend on epigenetic factors. Regulated changes in chromatin structure, directed by enhancers and promoter, can modify the availability of recombination signal sequences to the RAG recombinase. Regulated changes in locus conformation may control the synapsis of distant recombination signal sequences, and regulated changes in subnuclear positioning may influence locus recombination events by unknown mechanisms. Together these influences may explain the ordered activation and inactivation of T cell receptor locus recombination events, and the phenomenon of Tcrb allelic exclusion.

Krangel, Michael S.

2009-01-01

17

Identification of astrocytoma associated genes including cell surface markers  

PubMed Central

Background Despite intense effort the treatment options for the invasive astrocytic tumors are still limited to surgery and radiation therapy, with chemotherapy showing little or no increase in survival. The generation of Serial Analysis of Gene Expression (SAGE) profiles is expected to aid in the identification of astrocytoma-associated genes and highly expressed cell surface genes as molecular therapeutic targets. SAGE tag counts can be easily added to public expression databases and quickly disseminated to research efforts worldwide. Methods We generated and analyzed the SAGE transcription profiles of 25 primary grade II, III and IV astrocytomas [1]. These profiles were produced as part of the Cancer Genome Anatomy Project's SAGE Genie [2], and were used in an in silico search for candidate therapeutic targets by comparing astrocytoma to normal brain transcription. Real-time PCR and immunohistochemistry were used for the validation of selected candidate target genes in 2 independent sets of primary tumors. Results A restricted set of tumor-associated genes was identified for each grade that included genes not previously associated with astrocytomas (e.g. VCAM1, SMOC1, and thymidylate synthetase), with a high percentage of cell surface genes. Two genes with available antibodies, Aquaporin 1 and Topoisomerase 2A, showed protein expression consistent with transcript level predictions. Conclusions This survey of transcription in malignant and normal brain tissues reveals a small subset of human genes that are activated in malignant astrocytomas. In addition to providing insights into pathway biology, we have revealed and quantified expression for a significant portion of cell surface and extra-cellular astrocytoma genes.

Boon, Kathy; Edwards, Jennifer B; Eberhart, Charles G; Riggins, Gregory J

2004-01-01

18

Dopamine receptor genes: new tools for molecular psychiatry.  

PubMed Central

For over a decade it has been generally assumed that all the pharmacological and biochemical actions of dopamine within the central nervous system and periphery were mediated by two distinct dopamine receptors. These receptors, termed D1 and D2, were defined as those coupled to the stimulation or inhibition of adenylate cyclase, respectively, and by their selectivity and avidity for various drugs and compounds. The concept that two dopamine receptors were sufficient to account for all the effects mediated by dopamine was an oversimplification. Recent molecular biological studies have identified five distinct genes which encode at least eight functional dopamine receptors. The members of the expanded dopamine receptor family, however, can still be codifed by way of the original D1 and D2 receptor dichotomy. These include two genes encoding dopamine D1-like receptors (D1 [D1A]/D5 [D1B]) and three genes encoding D2-like receptors (D2/D3/D4). We review here our recent work on the cloning and characterization of some of the members of the dopamine receptor gene family (D1, D2, D4, D5), their relationship to neuropsychiatric disorders and their potential role in antipsychotic drug action. Images Fig. 1

Niznik, H B; Van Tol, H H

1992-01-01

19

Promoter architecture of mouse olfactory receptor genes.  

PubMed

Odorous chemicals are detected by the mouse main olfactory epithelium (MOE) by about 1100 types of olfactory receptors (OR) expressed by olfactory sensory neurons (OSNs). Each mature OSN is thought to express only one allele of a single OR gene. Major impediments to understand the transcriptional control of OR gene expression are the lack of a proper characterization of OR transcription start sites (TSSs) and promoters, and of regulatory transcripts at OR loci. We have applied the nanoCAGE technology to profile the transcriptome and the active promoters in the MOE. nanoCAGE analysis revealed the map and architecture of promoters for 87.5% of the mouse OR genes, as well as the expression of many novel noncoding RNAs including antisense transcripts. We identified candidate transcription factors for OR gene expression and among them confirmed by chromatin immunoprecipitation the binding of TBP, EBF1 (OLF1), and MEF2A to OR promoters. Finally, we showed that a short genomic fragment flanking the major TSS of the OR gene Olfr160 (M72) can drive OSN-specific expression in transgenic mice. PMID:22194471

Plessy, Charles; Pascarella, Giovanni; Bertin, Nicolas; Akalin, Altuna; Carrieri, Claudia; Vassalli, Anne; Lazarevic, Dejan; Severin, Jessica; Vlachouli, Christina; Simone, Roberto; Faulkner, Geoffrey J; Kawai, Jun; Daub, Carsten O; Zucchelli, Silvia; Hayashizaki, Yoshihide; Mombaerts, Peter; Lenhard, Boris; Gustincich, Stefano; Carninci, Piero

2011-12-22

20

Promoter architecture of mouse olfactory receptor genes  

PubMed Central

Odorous chemicals are detected by the mouse main olfactory epithelium (MOE) by about 1100 types of olfactory receptors (OR) expressed by olfactory sensory neurons (OSNs). Each mature OSN is thought to express only one allele of a single OR gene. Major impediments to understand the transcriptional control of OR gene expression are the lack of a proper characterization of OR transcription start sites (TSSs) and promoters, and of regulatory transcripts at OR loci. We have applied the nanoCAGE technology to profile the transcriptome and the active promoters in the MOE. nanoCAGE analysis revealed the map and architecture of promoters for 87.5% of the mouse OR genes, as well as the expression of many novel noncoding RNAs including antisense transcripts. We identified candidate transcription factors for OR gene expression and among them confirmed by chromatin immunoprecipitation the binding of TBP, EBF1 (OLF1), and MEF2A to OR promoters. Finally, we showed that a short genomic fragment flanking the major TSS of the OR gene Olfr160 (M72) can drive OSN-specific expression in transgenic mice.

Plessy, Charles; Pascarella, Giovanni; Bertin, Nicolas; Akalin, Altuna; Carrieri, Claudia; Vassalli, Anne; Lazarevic, Dejan; Severin, Jessica; Vlachouli, Christina; Simone, Roberto; Faulkner, Geoffrey J.; Kawai, Jun; Daub, Carsten O.; Zucchelli, Silvia; Hayashizaki, Yoshihide; Mombaerts, Peter; Lenhard, Boris; Gustincich, Stefano; Carninci, Piero

2012-01-01

21

Chromosomal localization of prostanoid receptor genes  

SciTech Connect

Prostanoids such as prostaglandins (PGs) and thromboxane (TXA{sub 2}) are a family of oxygenated metabolites of arachidonic acid. They produce a wide variety of physiological and pathophysiological effects mediated through specific cell surface receptors. Recent cDNA cloning of the prostaglandins and thromboxane receptors indicates that they are a unique family of receptors within the superfamily of G-protein-coupled receptors. Not only are all the prostanoids (PGE{sub 2}, PGF{sub 2{alpha}}, PGI{sub 2}, PGD{sub 2} and TXA{sub 2}) structurally related, but their receptors also show significant (26-47%) amino acid sequence identity. To investigate the evolutionary relationship between the various prostanoid receptors and their involvement in a number of pathophysiological conditions, we have mapped these loci in the human genome. The PGE{sub 2} receptor subtypes Ep{sub 1}, EP{sub 2}, EP{sub 3}, the PGF{sub 2{alpha}} receptor (FP), the PGI{sub 2} receptor (IP) and the TXA{sub 2} receptor (Tbxa2r) were sublocalized by in situ hybridization. EP{sub 1},IP and Tbxa2r were mapped to chromosome 19 at 19p13.1, 19q13.3 and 19p13.3, respectively. EP{sub 3} and FP mapped to 1p13.2 and 1p13.1, respectively. EP{sub 2} mapped to 5p13.1. Mapping the genomic loci of the prostanoid receptor family genes should expand our understanding of the evolution of G-protein-coupled receptor family genes and advance our investigation of the involvement of these genes in various pathophysiological conditions.

Adam, M.A.; Abramovitz, M.; Anderson, L.L. [Merck Frosst Centre for Therapeutic Research, Kirkland, Quebec (Canada)] [and others

1994-09-01

22

Widespread ectopic expression of olfactory receptor genes  

Microsoft Academic Search

BACKGROUND: Olfactory receptors (ORs) are the largest gene family in the human genome. Although they are expected to be expressed specifically in olfactory tissues, some ectopic expression has been reported, with special emphasis on sperm and testis. The present study systematically explores the expression patterns of OR genes in a large number of tissues and assesses the potential functional implication

Ester Feldmesser; Tsviya Olender; Miriam Khen; Itai Yanai; Ron Ophir; Doron Lancet

2006-01-01

23

Chromosome 11: gene for dopamine receptors, Matt RidleySite: DNA Interactive (www.dnai.org)  

NSDL National Science Digital Library

Interviewee: Matt Ridley DNAi Location:Genome>tour>genome spots>Dopamine receptor Location: chromosome 11 gene name: D4DR (dopamine receptor) This gene on chromosome 11 appears to influence personality. The protein produced from this gene is a receptor for the neurotransmitter dopamine. Dopamine pathways control many aspects of the brain, including blood flow. If this gene contains many repeated sequences the person is less responsive to dopamine and more likely to seek external "thrills" in their lives.

2008-10-06

24

Contrasting Modes of Evolution Between Vertebrate Sweet\\/Umami Receptor Genes and Bitter Receptor Genes  

Microsoft Academic Search

ABSTRACT Taste reception is fundamental to diet selection in many animals. The genetic basis underlying the evolution and diversity of taste reception, however, is not well understood. Recent discoveries of T1R sweet\\/umami receptor genes and T2R bitter receptor genes in humans and mice provided an opportunity to address this question.

Peng Shi; Jianzhi Zhang

2005-01-01

25

Estrogen receptor genes variations and breast cancer risk in Iran.  

PubMed

Evidence suggests that alterations in estrogen signaling pathways, including estrogen receptor ? (ER-?) and estrogen receptor ? (ER-?) occur during breast cancer development. ER-? and ER-? genes polymorphisms have been found to be associated with breast cancer and clinical features of the disease in the western countries. In the current study, we evaluated the hypothesis that certain sequence variants of the ER-? and ER-? genes are associated with an additively increased risk for breast cancer in Iranian women breast cancer patients. The genes were scanned in 150 Iranian patients with newly diagnosed invasive breast tumors and in healthy control individuals by PCR single-strand conformation polymorphism (SSCP) method. Three single nucleotide polymorphisms (SNPs) in codon10 (TCT?TCC), codon 352 (CCG?CCC) and codon 594 (ACG?ACA) in ER-? gene and one SNP codon 392 (CTC?CTG) in ER-? were revealed have additive effects in developing breast cancer and LN metastases. Also, SNP in codon 392 of estrogen receptor-? gene is more effective (threefold) than those SNPs in codons 10, 325, 594 of estrogen receptor-? gene in developing LN metastases in breast cancer patients. SNPs in estrogen receptor ? and ? have additive effects in increasing risk for developing breast cancer with LN metastases among Iranian women breast cancer patients. PMID:22993654

Abbasi, Sakineh; Nouri, Mehrnaz; Azimi, Cyrus

2012-08-25

26

Reciprocal activation of Xenobiotic response genes by nuclear receptors SXR\\/PXR and CAR  

Microsoft Academic Search

The cytochrome P450 (CYP) gene products such as CYP3A and CYP2B are essential for the metabolism of steroid hormones and xenochemicals including prescription drugs. Nuclear receptor SXR\\/PXR (steroid and xenobiotic receptor\\/pregnenolone X receptor) has been shown both biochemically and genetically to activate CYP3A genes, while similar studies have established constitutive androstane receptor (CAR) as a CYP2B regulator. The response elements

Wen Xie; Joyce L. Barwick; Cynthia M. Simon; Alexis M. Pierce; Stephen Safe; Bruce Blumberg; Philip S. Guzelian; Ronald M. Evans

2000-01-01

27

Quantitative set analysis for gene expression: a method to quantify gene set differential expression including gene-gene correlations.  

PubMed

Enrichment analysis of gene sets is a popular approach that provides a functional interpretation of genome-wide expression data. Existing tests are affected by inter-gene correlations, resulting in a high Type I error. The most widely used test, Gene Set Enrichment Analysis, relies on computationally intensive permutations of sample labels to generate a null distribution that preserves gene-gene correlations. A more recent approach, CAMERA, attempts to correct for these correlations by estimating a variance inflation factor directly from the data. Although these methods generate P-values for detecting gene set activity, they are unable to produce confidence intervals or allow for post hoc comparisons. We have developed a new computational framework for Quantitative Set Analysis of Gene Expression (QuSAGE). QuSAGE accounts for inter-gene correlations, improves the estimation of the variance inflation factor and, rather than evaluating the deviation from a null hypothesis with a P-value, it quantifies gene-set activity with a complete probability density function. From this probability density function, P-values and confidence intervals can be extracted and post hoc analysis can be carried out while maintaining statistical traceability. Compared with Gene Set Enrichment Analysis and CAMERA, QuSAGE exhibits better sensitivity and specificity on real data profiling the response to interferon therapy (in chronic Hepatitis C virus patients) and Influenza A virus infection. QuSAGE is available as an R package, which includes the core functions for the method as well as functions to plot and visualize the results. PMID:23921631

Yaari, Gur; Bolen, Christopher R; Thakar, Juilee; Kleinstein, Steven H

2013-08-05

28

Quantitative set analysis for gene expression: a method to quantify gene set differential expression including gene-gene correlations  

PubMed Central

Enrichment analysis of gene sets is a popular approach that provides a functional interpretation of genome-wide expression data. Existing tests are affected by inter-gene correlations, resulting in a high Type I error. The most widely used test, Gene Set Enrichment Analysis, relies on computationally intensive permutations of sample labels to generate a null distribution that preserves gene–gene correlations. A more recent approach, CAMERA, attempts to correct for these correlations by estimating a variance inflation factor directly from the data. Although these methods generate P-values for detecting gene set activity, they are unable to produce confidence intervals or allow for post hoc comparisons. We have developed a new computational framework for Quantitative Set Analysis of Gene Expression (QuSAGE). QuSAGE accounts for inter-gene correlations, improves the estimation of the variance inflation factor and, rather than evaluating the deviation from a null hypothesis with a P-value, it quantifies gene-set activity with a complete probability density function. From this probability density function, P-values and confidence intervals can be extracted and post hoc analysis can be carried out while maintaining statistical traceability. Compared with Gene Set Enrichment Analysis and CAMERA, QuSAGE exhibits better sensitivity and specificity on real data profiling the response to interferon therapy (in chronic Hepatitis C virus patients) and Influenza A virus infection. QuSAGE is available as an R package, which includes the core functions for the method as well as functions to plot and visualize the results.

Yaari, Gur; Bolen, Christopher R.; Thakar, Juilee; Kleinstein, Steven H.

2013-01-01

29

Cereal genes similar to Snf2 define a new subfamily that includes human and mouse genes.  

PubMed

Genes from the SNF2 family play important roles in transcriptional regulation, maintenance of chromosome integrity and DNA repair. This study describes the molecular cloning and characterization of cereal genes from this family. The predicted proteins exhibit a novel C-terminal domain that defines a new subfamily designated SNF2P that includes human and mouse proteins. Comparison between genomic and cDNA sequences showed that cereal Snf2P genes consisted of 17 exons, including one only 8 bp long. Two barley alleles differed by the presence of a 7.7-kb non-LTR retrotransposon in intron 6. An alternative annotation of the orthologous Arabidopsis gene would improve its similarity with the other members of the subfamily. Intron 2 was not spliced out in approximately half of the rice Snf2P mRNAs present in leaves, resulting in a premature stop codon. Transcripts from the barley and wheat Snf2P genes were found in apexes, leaves, sheaths, roots and spikes. The Snf2P genes exist as single copies on wheat chromosome arm 5A(m)L and in the colinear regions on barley chromosome arm 4HL and rice chromosome 3. High-density genetic mapping and RT-PCR suggest that Snf2P is not a candidate gene for the tightly linked vernalization gene Vrn2. PMID:12471446

Yan, L; Echenique, V; Busso, C; SanMiguel, P; Ramakrishna, W; Bennetzen, J L; Harrington, S; Dubcovsky, J

2002-10-24

30

Androgen receptor gene and male infertility  

Microsoft Academic Search

Androgens are critical steroid hormones that determine the expression of the male phenotype. Their actions are mediated by a single androgen receptor (AR) which, upon ligand binding, translocates to the nucleus to regulate the expression of androgen-responsive genes. Mutations that disrupt AR function totally result in the complete feminization of 46 XY individuals and the complete androgen insensitivity syndrome. Studies

E. L. Yong; C. J. Loy; K. S. Sim

2003-01-01

31

Glucose Regulation of the Expression of the Glucagon Receptor Gene  

Microsoft Academic Search

The glucagon receptor gene is a member of a gene family, the expression of which is strongly upregulated by glucose. This review deals with the structure of both the glucagon receptor gene and its promoter. Attention is focused on the glucose regulatory element that we discovered in the promoter of this gene. Regulation by glucose of genes implicated in glucose

Michal Svoboda; Laurence Portois; Willy J. Malaisse

1999-01-01

32

Mutations including the promoter region of myocilin\\/TIGR gene  

Microsoft Academic Search

Mutations in the MYOC\\/TIGR gene are responsible for autosomal dominant primary open angle glaucoma (POAG). Almost all mutations responsible for POAG have been detected in the coding region (in particular at exon 3). By using the techniques of PCR, SSCP, automated sequencing and restriction analysis, we have studied 79 patients suffering from glaucoma. We have found five patients with sequence

Maria Saura; Montse Cabana; Carmen Ayuso; Diana Valverde

2005-01-01

33

Extrasynaptic NMDA Receptors Reshape Gene Ranks  

NSDL National Science Digital Library

The N-methyl-D-aspartate (NMDA) subtype of glutamate receptors (NMDAR) plays a key role in the control of neuronal plasticity and cell survival by modifying the activity of different signaling pathways and numerous genes. However, it remains unclear how the activation of this one class of glutamate receptors can lead to different functional consequences, such as enhancement of neuronal survival or induction of neuronal death. Recent work further refines the hypothesis that synaptic and extrasynaptic NMDARs have distinct roles in neuronal survival and death by showing that these two subpopulations of NMDARs differentially modify whole-genome activity.

Igor Medina (INSERM;Mediterranean Institute of Neurobiology (INMED) REV)

2007-05-15

34

[Frontotemporal dementia (FTD) and genetic mutations including progranulin gene].  

PubMed

Research on familial frontotemporal lobar degeneration (FTLD) has led to the discovery of disease-causing genes: microtubule-associated protein tau (MAPT), progranulin (PGRN) and valosin-containing protein (VCP). TAR DNA-binding protein of 43 kDa (TDP-43) has been identified as a major component of tau-negative ubiquitin-positive inclusions in familial and sporadic FTLD and amyotrophic lateral sclerosis (ALS), which are now referred to as TDP-43 proteinopathy. Recent findings of mutations in TDP-43 gene in familial and sporadic ALS cases confirm the pathogenetic role for TDP-43 in neurodegeneration. TDP-43 proteinopathies have been classified into 4 pathological subtypes. Type 1 is characterized by numerous dystrophic neurites (DNs), Type 2 has numerous neuronal cytoplasmic inclusions (NCIs), Type 3 has NCIs and DNs and Type 4 has neuronal intranuclear inclusions (NIIs) and DNs. There is a close relationship between such pathological subtypes of TDP-43 proteinopathy and the immunoblot pattern of C-terminal fragments of accumulated TDP-43. These results parallel our earlier findings of differing C-terminal tau fragments in progressive supranuclear palsy and corticobasal degeneration, despite identical composition of tau isoforms. Taken together, these results suggest that elucidating the mechanism of C-terminal fragment origination may shed light on the pathogenesis of several neurodegenerative disorders involving TDP-43 proteinopathy and tauopathy. PMID:19198141

Arai, Tetsuaki; Hasegawa, Masato; Nishihara, Masugi; Nonaka, Takashi; Kametani, Fuyuki; Yoshida, Mari; Hashizume, Yoshio; Beach, Thomas G; Morita, Mitsuya; Nakano, Imaharu; Oda, Tatsuro; Tsuchiya, Kuniaki; Akiyama, Haruhiko

2008-11-01

35

Thyroid Hormone Receptor Genes of Neotenic Amphibians  

Microsoft Academic Search

.   Since thyroid hormones play a pivotal role in amphibian metamorphosis we used PCR to amplify DNA fragments corresponding\\u000a to a portion of the ligand-binding domain of the thyroid hormone receptor (TR) genes in several neotenic amphibians: the obligatory\\u000a neotenic members of the family Proteidea the mudpuppy Necturus maculosus and Proteus anguinus as well as two members of the facultative

Rachid Safi; Agnès Begue; Catherine Hänni; Dominique Stehelin; Jamshed R. Tata; Vincent Laudet

1997-01-01

36

Adrenergic Receptor Signaling Components in Gene Therapy  

Microsoft Academic Search

Adrenergic receptor (AR) signaling is a key regulator of normal cardiopulmonary homeostasis. Under pathophysiological conditions,\\u000a such as heart failure, asthma, and hypertension, there are alterations in the signaling cascades. Advances in the ability\\u000a to manipulate the adenoviral genome have allowed the development of gene therapy in which transgenes of interest are inserted\\u000a into the adenovirus and transferred to mammals in

Andrea D. Eckhart; Walter J. Koch

37

Human chromosome 11 DNA sequence and analysis including novel gene identification  

Microsoft Academic Search

Chromosome 11, although average in size, is one of the most gene- and disease-rich chromosomes in the human genome. Initial gene annotation indicates an average gene density of 11.6 genes per megabase, including 1,524 protein-coding genes, some of which were identified using novel methods, and 765 pseudogenes. One-quarter of the protein-coding genes shows overlap with other genes. Of the 856

Hideki Noguchi; Yasushi Totoki; Atsushi Toyoda; Yoko Kuroki; Ken Dewar; Christine Lloyd; Takehiko Itoh; Tadayuki Takeda; Dae-Won Kim; Xinwei She; Karen F. Barlow; Toby Bloom; Elspeth Bruford; Jean L. Chang; Christina A. Cuomo; Evan Eichler; Michael G. FitzGerald; David B. Jaffe; Kurt LaButti; Robert Nicol; Hong-Seog Park; Christopher Seaman; Carrie Sougnez; Xiaoping Yang; Andrew R. Zimmer; Michael C. Zody; Bruce W. Birren; Chad Nusbaum; Asao Fujiyama; Masahira Hattori; Jane Rogers; Eric S. Lander; Todd D. Taylor; Yoshiyuki Sakaki

2006-01-01

38

Skeletal muscle denervation activates acetylcholine receptor genes  

PubMed Central

Transcriptional activity of acetylcholine receptor subunit genes was investigated in innervated and denervated chick skeletal muscle. The sciatic nerve of 3-d-old White Leghorn chicks was sectioned unilaterally; after various intervals, nuclei were isolated from operated and sham-operated animals, and run-on assays performed. Nuclei were incubated with 32P-UTP, and total RNA was extracted and hybridized onto filters containing an excess of subunit-specific DNA. Specific transcripts were detected by autoradiography and quantitated densitometrically. A sharp increase in transcriptional activity was observed to begin approximately 1/2 d after the operation and peak 1 d later when transcriptional rates reached approximately seven-, six-, and fivefold control levels for the alpha-, delta-, and gamma-subunit genes, respectively. The specificity of the effect was ascertained by normalization to total RNA synthesis and by the demonstration that several nonreceptor genes respond differently to denervation. These results suggest that a denervation signal reaches the genome to induce receptor expression. In addition, since the increase in mRNA levels significantly exceeds what can be accounted for by increased gene activity, posttranscriptional effects are suggested.

1989-01-01

39

Regulation of Mouse k Opioid Receptor Gene Expression by Retinoids  

Microsoft Academic Search

The effect of retinoids on the expression of k opioid receptor (KOR) gene was examined in normal and transgenic animals. KOR-lacZ transgene expression was specifically elevated in KOR-positive areas of the developing CNS by depleting vitamin A from animal diets. The endogenous KOR mRNA species, including all three isoforms, were also upregulated by depleting vitamin A in developing animals. Change

Jing Bi; Xinli Hu; Horace H. Loh; Li-Na Wei

2001-01-01

40

The olfactory receptor gene superfamily: data mining, classification, and nomenclature  

Microsoft Academic Search

.   The vertebrate olfactory receptor (OR) subgenome harbors the largest known gene family, which has been expanded by the need\\u000a to provide recognition capacity for millions of potential odorants. We implemented an automated procedure to identify all\\u000a OR coding regions from published sequences. This led us to the identification of 831 OR coding regions (including pseudogenes)\\u000a from 24 vertebrate species.

Gustavo Glusman; Anita Bahar; Dror Sharon; Yitzhak Pilpel; Julia White; Doron Lancet

2000-01-01

41

Social dominance regulates androgen and estrogen receptor gene expression  

Microsoft Academic Search

In Astatotilapia burtoni, dominant males have higher levels of sex steroid hormones than subordinate males. Because of the complex regulatory interactions between steroid hormones and receptors, we asked whether dominance is also associated with variation in sex steroid receptor gene expression. Using quantitative PCR, we compared the expression of specific subtypes of androgen (AR) and estrogen (ER) receptor genes between

Sabrina S. Burmeister; Vinita Kailasanath; Russell D. Fernald

2007-01-01

42

The Evolution of Mammalian Olfactory Receptor Genes  

PubMed Central

We performed a comparative study of four subfamilies of olfactory receptor genes first identified in the dog to assess changes in the gene family during mammalian evolution, and to begin linking the dog genetic map to that of humans. The human subfamilies were localized to chromosomes 7, 11, and 19. The two subfamilies that were tightly linked in the dog genome were also tightly linked in the human genome. The four subfamilies were compared in human (primate), horse (perissodactyl), and a variety of artiodactyls and carnivores. Some changes in gene number were detected, but overall subfamily size appeared to have been established before the divergence of these mammals 60-100 million years ago.

Issel-Tarver, L.; Rine, J.

1997-01-01

43

Molecular structure of the human gonadotropin-releasing hormone receptor gene  

Microsoft Academic Search

GnRH receptors belong to the family of G protein-coupled receptor proteins and have been localized to the anterior pituitary, brain and reproductive organs as well as many steroid-dependent tumor tissues. Recently, cDNAs for the GnRH receptors of several species including the human have been cloned. To determine the structure of the gene encoding the human GnRH receptor, we isolated the

Sham S Kakar

1997-01-01

44

Peroxisome Proliferator-Activated Receptor g-Dependent Repression of the Inducible Nitric Oxide Synthase Gene  

Microsoft Academic Search

The peroxisome proliferator-activated receptor g (PPARg) is a member of the nuclear receptor superfamily that activates target gene transcription in a ligand-dependent manner. In addition, liganded PPARg can inhib- it transcription of genes induced by gamma interferon (IFN-g) and\\/or lipopolysaccharides (LPSs), including the inducible nitric oxide synthase (iNOS) gene. Inhibition of the iNOS promoter is achieved partially through an- tagonizing

MEI LI; GABRIEL PASCUAL; CHRISTOPHER K. GLASS

2000-01-01

45

Genes affecting the activity of nicotinic receptors involved in Caenorhabditis elegans egg-laying behavior.  

PubMed Central

Egg-laying behavior in Caenorhabditis elegans is regulated by multiple neurotransmitters, including acetylcholine and serotonin. Agonists of nicotinic acetylcholine receptors such as nicotine and levamisole stimulate egg laying; however, the genetic and molecular basis for cholinergic neurotransmission in the egg-laying circuitry is not well understood. Here we describe the egg-laying phenotypes of eight levamisole resistance genes, which affect the activity of levamisole-sensitive nicotinic receptors in nematodes. Seven of these genes, including the nicotinic receptor subunit genes unc-29, unc-38, and lev-1, were essential for the stimulation of egg laying by levamisole, though they had only subtle effects on egg-laying behavior in the absence of drug. Thus, these genes appear to encode components of a nicotinic receptor that can promote egg laying but is not necessary for egg-laying muscle contraction. Since the levamisole-receptor mutants responded to other cholinergic drugs, other acetylcholine receptors are likely to function in parallel with the levamisole-sensitive receptors to mediate cholinergic neurotransmission in the egg-laying circuitry. In addition, since expression of functional unc-29 in muscle cells restored levamisole sensitivity under some but not all conditions, both neuronal and muscle cell UNC-29 receptors are likely to contribute to the regulation of egg-laying behavior. Mutations in one levamisole receptor gene, unc-38, also conferred both hypersensitivity and reduced peak response to serotonin; thus nicotinic receptors may play a role in regulating serotonin response pathways in the egg-laying neuromusculature.

Kim, J; Poole, D S; Waggoner, L E; Kempf, A; Ramirez, D S; Treschow, P A; Schafer, W R

2001-01-01

46

Widespread ectopic expression of olfactory receptor genes  

PubMed Central

Background Olfactory receptors (ORs) are the largest gene family in the human genome. Although they are expected to be expressed specifically in olfactory tissues, some ectopic expression has been reported, with special emphasis on sperm and testis. The present study systematically explores the expression patterns of OR genes in a large number of tissues and assesses the potential functional implication of such ectopic expression. Results We analyzed the expression of hundreds of human and mouse OR transcripts, via EST and microarray data, in several dozens of human and mouse tissues. Different tissues had specific, relatively small OR gene subsets which had particularly high expression levels. In testis, average expression was not particularly high, and very few highly expressed genes were found, none corresponding to ORs previously implicated in sperm chemotaxis. Higher expression levels were more common for genes with a non-OR genomic neighbor. Importantly, no correlation in expression levels was detected for human-mouse orthologous pairs. Also, no significant difference in expression levels was seen between intact and pseudogenized ORs, except for the pseudogenes of subfamily 7E which has undergone a human-specific expansion. Conclusion The OR superfamily as a whole, show widespread, locus-dependent and heterogeneous expression, in agreement with a neutral or near neutral evolutionary model for transcription control. These results cannot reject the possibility that small OR subsets might play functional roles in different tissues, however considerable care should be exerted when offering a functional interpretation for ectopic OR expression based only on transcription information.

Feldmesser, Ester; Olender, Tsviya; Khen, Miriam; Yanai, Itai; Ophir, Ron; Lancet, Doron

2006-01-01

47

Identification of a family of muscarinic acetylcholine receptor genes  

SciTech Connect

Complementary DNAs for three different muscarinic acetylcholine receptors were isolated from a rat cerebral cortex library, and the cloned receptors were expressed in mammalian cells. Analysis of human and rat genomic clones indicates that there are at least four functional muscarinic receptor genes and that these genes lack introns in the coding sequence. This gene family provides a new basis for evaluating the diversity of muscarinic mechanisms in the nervous system.

Bonner, T.I.; Buckley, N.J.; Young, A.C.; Brann, M.R.

1987-07-31

48

Genetic and Epigenetic Alterations of Lysophosphatidic Acid Receptor Genes in Rodent Tumors by Experimental Models  

PubMed Central

Lysophosphatidic acid (LPA) is a bioactive mediator and induces several biological effects, including cell proliferation, migration, morphogenesis and differentiation. LPA interacts with at least six G protein-coupled receptors (GPCRs), including LPA receptor-1 (LPA1), LPA2, LPA3, LPA4, LPA5 and LPA6. These receptors show different biological functions through the binding of LPA, depending on the type of cells. In human malignancies, a high level of LPA production was found in plasma and ascites in ovarian cancer cases. Moreover, aberrant expression levels of LPA receptor genes were detected in some cancer cells. Therefore, it is suggested that LPA receptors may be involved in the pathogenesis of tumor cells as well as LPA per se. Recently, we have reported that alterations of LPA receptor genes also occur in rodent tumors. In this review, we summarize the recent evidence in the investigations of LPA receptor alterations in rodent tumors by experimental models.

Tsujiuchi, Toshifumi; Okabe, Kyoko; Fukushima, Nobuyuki

2011-01-01

49

GPR48 Increases Mineralocorticoid Receptor Gene Expression  

PubMed Central

Aldosterone and the mineralocorticoid receptor (MR) are critical to the maintenance of electrolyte and BP homeostasis. Mutations in the MR cause aldosterone resistance known as pseudohypoaldosteronism type 1 (PHA1); however, some cases consistent with PHA1 do not exhibit known gene mutations, suggesting the possibility of alternative genetic variants. We observed that G protein–coupled receptor 48 (Gpr48/Lgr4) hypomorphic mutant (Gpr48m/m) mice had hyperkalemia and increased water loss and salt excretion despite elevated plasma aldosterone levels, suggesting aldosterone resistance. When we challenged the mice with a low-sodium diet, these features became more obvious; the mice also developed hyponatremia and increased renin expression and activity, resembling a mild state of PHA1. There was marked renal downregulation of MR and its downstream targets (e.g., the ?-subunit of the amiloride-sensitive epithelial sodium channel), which could provide a mechanism for the aldosterone resistance. We identified a noncanonical cAMP-responsive element located in the MR promoter and demonstrated that GPR48 upregulates MR expression via the cAMP/protein kinase A pathway in vitro. Taken together, our data demonstrate that GPR48 enhances aldosterone responsiveness by activating MR expression, suggesting that GPR48 contributes to homeostasis of electrolytes and BP and may be a candidate gene for PHA1.

Wang, Jiqiu; Li, Xiaoying; Ke, Yingying; Lu, Yan; Wang, Feng; Fan, Nengguang; Sun, Haiyan; Zhang, Huijie; Liu, Ruixin; Yang, Jun; Ye, Lei; Liu, Mingyao

2012-01-01

50

GPR48 increases mineralocorticoid receptor gene expression.  

PubMed

Aldosterone and the mineralocorticoid receptor (MR) are critical to the maintenance of electrolyte and BP homeostasis. Mutations in the MR cause aldosterone resistance known as pseudohypoaldosteronism type 1 (PHA1); however, some cases consistent with PHA1 do not exhibit known gene mutations, suggesting the possibility of alternative genetic variants. We observed that G protein-coupled receptor 48 (Gpr48/Lgr4) hypomorphic mutant (Gpr48(m/m)) mice had hyperkalemia and increased water loss and salt excretion despite elevated plasma aldosterone levels, suggesting aldosterone resistance. When we challenged the mice with a low-sodium diet, these features became more obvious; the mice also developed hyponatremia and increased renin expression and activity, resembling a mild state of PHA1. There was marked renal downregulation of MR and its downstream targets (e.g., the ?-subunit of the amiloride-sensitive epithelial sodium channel), which could provide a mechanism for the aldosterone resistance. We identified a noncanonical cAMP-responsive element located in the MR promoter and demonstrated that GPR48 upregulates MR expression via the cAMP/protein kinase A pathway in vitro. Taken together, our data demonstrate that GPR48 enhances aldosterone responsiveness by activating MR expression, suggesting that GPR48 contributes to homeostasis of electrolytes and BP and may be a candidate gene for PHA1. PMID:22135314

Wang, Jiqiu; Li, Xiaoying; Ke, Yingying; Lu, Yan; Wang, Feng; Fan, Nengguang; Sun, Haiyan; Zhang, Huijie; Liu, Ruixin; Yang, Jun; Ye, Lei; Liu, Mingyao; Ning, Guang

2011-12-01

51

The S15 self-incompatibility haplotype in Brassica oleracea includes three S gene family members expressed in stigmas.  

PubMed Central

Self-incompatibility in Brassica is controlled by a single, highly polymorphic locus that extends over several hundred kilobases and includes several expressed genes. Two stigma proteins, the S locus receptor kinase (SRK) and the S locus glycoprotein (SLG), are encoded by genes located at the S locus and are thought to be involved in the recognition of self-pollen by the stigma. We report here that two different SLG genes, SLGA and SLGB, are located at the S locus in the class II, pollen-recessive S15 haplotype. Both genes are interrupted by a single intron; however, SLGA encodes both soluble and membrane-anchored forms of SLG, whereas SLGB encodes only soluble SLG proteins. Thus, including SRK, the S locus in the S15 haplotype contains at least three members of the S gene family. The protein products of these three genes have been characterized, and each SLG glycoform was assigned to an SLG gene. Evidence is presented that the S2 and S5 haplotypes carry only one or the other of the SLG genes, indicating either that they are redundant or that they are not required for the self-incompatibility response.

Cabrillac, D; Delorme, V; Garin, J; Ruffio-Chable, V; Giranton, J L; Dumas, C; Gaude, T; Cock, J M

1999-01-01

52

Glucocorticoid receptor gene polymorphism and juvenile idiopathic arthritis  

Microsoft Academic Search

BACKGROUND: The glucocorticoid receptor gene (NR3C1) has been suggested as a candidate gene affecting juvenile idiopathic arthritis (JIA) course and prognosis. The purpose of this study is to investigate the glucocorticoid receptor gene BclI polymorphism (rs41423247) in JIA patients, the gene's role in susceptibility to juvenile idiopathic arthritis, and its associations with JIA activity, course and bone mineralization. METHODS: One

Mikhail M Kostik; Alexandra A Klyushina; Mikhail V Moskalenko; Larisa A Scheplyagina; Valentina I Larionova

2011-01-01

53

An epigenetic trap involved in olfactory receptor gene choice.  

PubMed

Reporting recently in Cell, Lyons et al. (2013) reveal key roles for transient LSD1 histone demethylase activity in activation of a single olfactory receptor allele and suppression of the rest of the olfactory receptor gene family, thereby locking in the expression of a single olfactory receptor per sensory neuron. PMID:23906063

Reinsborough, Calder; Chess, Andrew

2013-07-29

54

Induction of Human Liver X Receptor   Gene Expression Via an Autoregulatory Loop Mechanism  

Microsoft Academic Search

The liver X receptors (LXRs), members of the nu- clear receptor superfamily, play an important role in controlling lipid homeostasis by activating sev- eral genes involved in reverse cholesterol trans- port. These include members of the ATP binding cassette (ABC) superfamily of transporter proteins ABCA1 and ABCG1, surface constituents of plasma lipoproteins like apolipoprotein E, and cho- lesterol ester transport

YU LI; CHARLES BOLTEN; B. GANESH BHAT; JESSICA WOODRING-DIETZ; SUZHEN LI; SUDHIRDAS K. PRAYAGA; CHUNSHENG XIA; DEEPAK S. LALA; Pharmacia Corp

2002-01-01

55

Association of dopamine D2 receptor and leptin receptor genes with clinically severe obesity.  

PubMed

OBJECTIVE: The brain reward circuits that promote drug abuse may also be involved in pleasure seeking behavior and food cravings observed in severely obese subjects. Drug addiction polymorphisms such as the TaqI A1 allele of the dopamine D2 receptor (DRD2) are associated with cocaine, alcohol, and opioid use, but few studies have linked DRD2 to food craving. Other genes such as the leptin receptor gene (LEPR) and mu-opioid receptor gene (OPRM1) that affect appetite and pleasure centers in the brain may also influence food addiction and obesity. The three genes together may function synergistically. DESIGN AND METHODS: To evaluate associations between candidate genes, food craving, overeating, and BMI, we administered questionnaires including Power of Food Scale and Food Craving Inventory, conducted anthropometric measures, and collected blood from patients undergoing weight-loss treatment. Questionnaires and DNA specimens were collected for 80 participants. RESULTS: Participants were mostly female (74%) and Caucasian (79%), with an average age of 53 years old. Mean BMI for all participants was 43 kg/m(2) and was significantly associated in a linear fashion with Food Craving Inventory scores (P=0.0001) and Power of Food (P=0.02). The DRD2 TaqI A1 allele was significantly associated with BMI (P=0.04), while LEPR Lys109Arg and OPRM1 A118G variants were not. We stratified DRD2 by LEPR and OPRM1, and observed a significant interaction (P = 0.04) between DRD2 and LEPR, and a marginally significant interaction (P=0.06) between DRD2 and OPRM1. CONCLUSION: Genes associated with addictive behavior and appetite control may therefore, in combination, markedly influence development of clinically severe obesity. PMID:23670889

Carpenter, Catherine L; Wong, Angela M; Li, Zhaoping; Noble, Ernest P; Heber, David

2012-11-29

56

The androgen receptor gene mutations database.  

PubMed

The current version of the androgen receptor (AR) gene mutations database is described. The total number of reported mutations has risen from 212 to 272. We have expanded the database: (i) by adding a large amount of new data on somatic mutations in prostatic cancer tissue; (ii) by defining a new constitutional phenotype, mild androgen insensitivity (MAI); (iii) by placing additional relevant information on an internet site (http://www.mcgill.ca/androgendb/ ). The database has allowed us to examine the contribution of CpG sites to the multiplicity of reports of the same mutation in different families. The database is also available from EMBL (ftp.ebi.ac.uk/pub/databases/androgen) or as a Macintosh Filemaker Pro or Word file (MC33@musica,mcgill.ca) PMID:9016528

Gottlieb, B; Trifiro, M; Lumbroso, R; Pinsky, L

1997-01-01

57

The androgen receptor gene mutations database.  

PubMed

The current version of the androgen receptor (AR) gene mutations database is described. We have added (if available) data on the androgen binding phenotype of the mutant AR, the clinical phenotype of the affected persons, the family history and whether the pathogenicity of a mutation has been proven. Exonic mutations are now listed in 5'-->3' sequence regardless of type and single base pair changes are presented in codon context. Splice site and intronic mutations are listed separately. The database has allowed us to substantiate and amplify the observation of mutational hot spots within exons encoding the AR androgen binding domain. The database is available from EML (ftp://www.ebi.ac.uk/pub/databases/androgen) or as a Macintosh Filemaker file (MC33@musica.mcgill.ca). PMID:8594566

Gottlieb, B; Trifiro, M; Lumbroso, R; Vasiliou, D M; Pinsky, L

1996-01-01

58

Dynamics of nuclear receptor target gene regulation  

Microsoft Academic Search

Ligand-regulated nuclear receptors, such as estrogen receptors, glucocorticoid receptor, vitamin D receptor, and peroxisome\\u000a proliferator-activated receptors, belong to the most widely studied and best understood transcription factors. Therefore,\\u000a the dynamic nature of transcriptional regulation was observed first with different members of the nuclear receptor superfamily,\\u000a but is now also extended to other transcription factors, such as nuclear factor ?B. Dynamic

Carsten Carlberg; Sabine Seuter

2010-01-01

59

Diverse growth hormone receptor gene mutations in Laron syndrome  

SciTech Connect

To better understand the molecular genetic basis and genetic epidemiology of Laron syndrome (growth-hormone insensitivity syndrome), the authors analysed the growth-hormone receptor (GHR) genes of seven unrelated affected individuals from the United States, South America, Europe, and Africa. They amplified all nine GHR gene exons and splice junctions from these individuals by PCR and screened the products for mutations by using denaturing gradient gel electrophoresis (DGGE). They identified a single GHR gene fragment with abnormal DGGE results for each affected individual, sequenced this fragment, and, in each case, identified a mutation likely to cause Laron syndrome, including two nonsense mutations (R43X and R217X), two splice-junction mutations, (189-1 G to T and 71+1 G to A), and two frameshift mutations (46 del TT and 230 del TA or AT). Only one of these mutations, R43X, has been previously reported. Using haplotype analysis, they determined that this mutation, which involves a CpG dinucleotide hot spot, likely arose as a separate event in this case, relative to the two prior reports of R43X. Aside from R43X, the mutations identified are unique to patients from particular geographic regions. Ten GHR gene mutations have now been described in this disorder. The authors conclude that Laron syndrome is caused by diverse GHR gene mutations, including deletions, RNA processing defects, translational stop codons, and missense codons. All the identified mutations involve the extracellular domain of the receptor, and most are unique to particular families or geographic areas. 35 refs., 3 figs., 1 tab.

Berg, M.A.; Francke, U. (Stanford Univ. School of Medicine, CA (United States)); Gracia, R.; Rosenbloom, A.; Toledo, S.P.A. (Univ. Autonoma, Madrid (Spain)); Chernausek, S. (Children's Hospital Medical Center, Cincinnati, OH (United States)); Guevara-Aguirre, J. (Institute of Endocrinology, Metabolism, and Reproduction, Quito (Ecuador)); Hopp, M. (Univ. of Witwatersrand, Johannesburg (South Africa)); Rosenbloom, A.; Argente, J. (Univ. of Florida, Gainesville (United States)); Toledo, S.P.A. (Univ. of Sao Paulo (Brazil))

1993-05-01

60

Cloning and Expression of the Moraxella catarrhalis Lactoferrin Receptor Genes  

Microsoft Academic Search

The lactoferrin receptor genes from two strains of Moraxella catarrhalis have been cloned and sequenced. The lfr genes are arranged as lbpB followed by lbpA, a gene arrangement found in lactoferrin and transferrin receptor operons from several bacterial species. In addition, a third open reading frame, orf3, is located one nucleotide downstream of lbpA. The deduced lactoferrin binding protein A

RUN-PAN DU; QIJUN WANG; YAN-PING YANG; ANTHONY B. SCHRYVERS; PELE CHONG; MICHEL H. KLEIN; SHEENA M. LOOSMORE

1998-01-01

61

Gene Transfer and Molecular Cloning of the Human NGF Receptor  

NASA Astrophysics Data System (ADS)

Nerve growth factor (NGF) and its receptor are important in the development of cells derived from the neural crest. Mouse L cell transformants have been generated that stably express the human NGF receptor gene transfer with total human DNA. Affinity cross-linking, metabolic labeling and immunoprecipitation, and equilibrium binding with 125I-labeled NGF revealed that this NGF receptor had the same size and binding characteristics as the receptor from human melanoma cells and rat PC12 cells. The sequences encoding the NGF receptor were molecularly cloned using the human Alu repetitive sequence as a probe. A cosmid clone that contained the human NGF receptor gene allowed efficient transfection and expression of the receptor.

Chao, Moses V.; Bothwell, Mark A.; Ross, Alonzo H.; Koprowski, Hilary; Lanahan, Anthony A.; Buck, C. Randall; Sehgal, Amita

1986-04-01

62

Estrogen receptors and their genes--potential markers of functional and production traits of farm animals.  

PubMed

Estrogen receptors, similarly as other nuclear receptors, are transcription factors, which after binding to a proper ligand (17beta-estradiol, estron or estriol) are capable of regulating transcription of target genes. Due to the functions that estrogens play in the regulation of reproduction, development of the mammary gland, growth and differentiation of cells, estrogen receptors and their genes are considered as candidate markers for production and functional traits in farm animals. Known are two isoforms of the estrogen receptor-alpha and beta. They are encoded by separate genes located on different chromosomes. The typical feature of all genes coding for nuclear receptors, including the ER genes, is the complex structure of their 5' regions. In the 5' region of the ERalpha gene of different species are located alternative exons that code for transcripts of different length with different 5'-UTR (untranslated region). The mRNA variants are created by the alternative splicing of the primary transcripts. We sequenced a 2853 bp of the bovine ER gene 5' region, including exons A, B, C and their promoters. Moreover, we found several polymorphic sites, differing by single nucleotide substitutions (SNPs), in the 5' regulatory region and in the coding region of the bovine ERalpha gene. PMID:17661162

Szreder, Tomasz; Zwierzchowski, Lech

2007-07-28

63

Characterization of a dwarf gene in Brassica rapa , including the identification of a candidate gene  

Microsoft Academic Search

Dwarf genes have been valuable for improving harvestable yield of several crop plants and may be useful in oilseed Brassica. We evaluated a dwarf gene, dwf2, from Brassica rapa in order to determine its phenotypic effects and genetic characteristics. The dwf2 mutant was insensitive to exogenous GA 3 for both plant height and flowering time, suggesting that it is not

A. Muangprom; T. C. Osborn

2004-01-01

64

Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety  

Microsoft Academic Search

The glucocorticoid receptor (Gr, encoded by the gene Grl1) controls transcription of target genes both directly by interaction with DNA regulatory elements and indirectly by cross-talk with other transcription factors. In response to various stimuli, including stress, glucocorticoids coordinate metabolic, endocrine, immune and nervous system responses and ensure an adequate profile of transcription. In the brain, Gr has been proposed

François Tronche; Christoph Kellendonk; Oliver Kretz; Peter Gass; Katrin Anlag; Paul C. Orban; Rudolf Bock; Rüdiger Klein; Günther Schütz

1999-01-01

65

Amplification and Expression of the Epidermal Growth Factor Receptor Gene in Human Glioma Xenografts1  

Microsoft Academic Search

Xenografts from eight malignant human gliomas were established in athymic mice and were used to study amplification and expression of the epidermal growth factor receptor (EGFR) gene. Tissue identity between biopsy and xenografts was confirmed by karyotypic profiles, which showed that each glioma xenograft retained structural abnormalities, including double minute chromosomes, present in the parent glioma. EGFR gene amplification was

Peter A. Humphrey; Albert J. Wong; Bert Vogelstein; Henry S. Friedman; Mark H. Werner; Dareil D. Bigner; Sandra H. Bigner

66

Regulation of cytochrome P450 (CYP) genes by nuclear receptors.  

PubMed Central

Members of the nuclear-receptor superfamily mediate crucial physiological functions by regulating the synthesis of their target genes. Nuclear receptors are usually activated by ligand binding. Cytochrome P450 (CYP) isoforms often catalyse both formation and degradation of these ligands. CYPs also metabolize many exogenous compounds, some of which may act as activators of nuclear receptors and disruptors of endocrine and cellular homoeostasis. This review summarizes recent findings that indicate that major classes of CYP genes are selectively regulated by certain ligand-activated nuclear receptors, thus creating tightly controlled networks.

Honkakoski, P; Negishi, M

2000-01-01

67

Class II cytokine receptor gene cluster is a major locus for hepatitis B persistence  

PubMed Central

Persistent hepatitis B virus infection is a major risk factor for hepatocellular carcinoma, the most frequent cancer in some developing countries. Up to 95% of those infected at birth and 15% of those infected after the neonatal period fail to clear hepatitis B virus, together resulting in ?350 million persistent carriers worldwide. Via a whole genome scan in Gambian families, we have identified a major susceptibility locus as a cluster of class II cytokine receptor genes on chromosome 21q22. Coding changes in two of these genes, the type I IFN receptor gene, IFN-AR2, and the IL-10RB gene that encodes a receptor chain for IL-10-related cytokines including the IFN-?s, are associated with viral clearance (haplotype P value = 0.0003), and in vitro assays support functional roles for these variants in receptor signaling.

Frodsham, Angela J.; Zhang, Lyna; Dumpis, Uga; Taib, Nor Azizah Mohd; Best, Steve; Durham, Andrew; Hennig, Branwen J. W.; Hellier, Simon; Knapp, Susanne; Wright, Mark; Chiaramonte, Maria; Bell, John I.; Graves, Mary; Whittle, Hilton C.; Thomas, Howard C.; Thursz, Mark R.; Hill, Adrian V. S.

2006-01-01

68

The ?3 subunit gene of the nicotinic acetylcholine receptor is a candidate gene for ethanol stimulation  

PubMed Central

Alcohol and nicotine are coabused, and preclinical and clinical data suggest that common genes may influence responses to both drugs. A gene in a region of mouse chromosome 9 that includes a cluster of three nicotinic acetylcholine receptor (nAChR) subunit genes influences the locomotor stimulant response to ethanol. The current studies first used congenic mice to confirm the influential gene on chromosome 9. Congenic F2 mice were then used to more finely map the location. Gene expression of the three subunit genes was quantified in strains of mice that differ in response to ethanol. Finally, the locomotor response to ethanol was examined in mice heterozygous for a null mutation of the ?3 nAChR subunit gene (Chrna3). Congenic data indicate that a gene on chromosome 9, within a 46 cM region that contains the cluster of nAChR subunit genes, accounts for 41% of the genetic variation in the stimulant response to ethanol. Greater expression of Chrna3 was found in whole brain and dissected brain regions relevant to locomotor behavior in mice that were less sensitive to ethanol-induced stimulation compared to mice that were robustly stimulated; the other two nAChR subunit genes in the gene cluster (?5 and ?4) were not differentially expressed. Locomotor stimulation was not expressed on the genetic background of Chrna3 heterozygous (+/?) and wild-type (+/+) mice; +/? mice were more sensitive than +/+ mice to the locomotor depressant effects of ethanol. Chrna3 is a candidate gene for the acute locomotor stimulant response to ethanol that deserves further examination.

Kamens, H. M.; McKinnon, C. S.; Li, N; Helms, M. L.; Belknap, J. K.; Phillips, T. J.

2009-01-01

69

Overrepresentation of a Gene Family Encoding Extracytoplasmic Solute Receptors in Bordetella  

PubMed Central

A family of genes that are likely to encode extracytoplasmic solute receptors is strongly overrepresented in several ?-proteobacteria, including Bordetella pertussis. This gene family, of which members have been called bug genes, contains some examples that are contained within polycistronic operons coding for tripartite uptake transporters of the TTT family, while the vast majority are “orphan” genes. Proteomic and functional analyses demonstrated that several of these genes are expressed in B. pertussis, and one is involved in citrate uptake. The bug genes probably form an ancient family that has been subjected to a large expansion in a restricted phylogenic group.

Antoine, Rudy; Jacob-Dubuisson, Francoise; Drobecq, Herve; Willery, Eve; Lesjean, Sarah; Locht, Camille

2003-01-01

70

Marfan syndrome with a complex chromosomal rearrangement including deletion of the FBN1 gene  

PubMed Central

Background The majority of Marfan syndrome (MFS) cases is caused by mutations in the fibrillin-1 gene (FBN1), mapped to chromosome 15q21.1. Only few reports on deletions including the whole FBN1 gene, detected by molecular cytogenetic techniques, were found in literature. Results We report here on a female patient with clinical symptoms of the MFS spectrum plus craniostenosis, hypothyroidism and intellectual deficiency who presents a 1.9 Mb deletion, including the FBN1 gene and a complex rearrangement with eight breakpoints involving chromosomes 6, 12 and 15. Discussion This is the first report of MFS with a complex chromosome rearrangement involving a deletion of FBN1 and contiguous genes. In addition to the typical clinical findings of the Marfan syndrome due to FBN1 gene haploinsufficiency, the patient presents features which may be due to the other gene deletions and possibly to the complex chromosome rearrangement.

2012-01-01

71

Gene expression signature of estrogen receptor ? status in breast cancer  

PubMed Central

Background Estrogens are known to regulate the proliferation of breast cancer cells and to modify their phenotypic properties. Identification of estrogen-regulated genes in human breast tumors is an essential step toward understanding the molecular mechanisms of estrogen action in cancer. To this end we generated and compared the Serial Analysis of Gene Expression (SAGE) profiles of 26 human breast carcinomas based on their estrogen receptor ? (ER) status. Thus, producing a breast cancer SAGE database of almost 2.5 million tags, representing over 50,000 transcripts. Results We identified 520 transcripts differentially expressed between ER?-positive (+) and ER?-negative (-) primary breast tumors (Fold change ? 2; p < 0.05). Furthermore, we identified 220 high-affinity Estrogen Responsive Elements (EREs) distributed on the promoter regions of 163 out of the 473 up-modulated genes in ER? (+) breast tumors. In brief, we observed predominantly up-regulation of cell growth related genes, DNA binding and transcription factor activity related genes based on Gene Ontology (GO) biological functional annotation. GO terms over-representation analysis showed a statistically significant enrichment of various transcript families including: metal ion binding related transcripts (p = 0.011), calcium ion binding related transcripts (p = 0.033) and steroid hormone receptor activity related transcripts (p = 0.031). SAGE data associated with ER? status was compared with reported information from breast cancer DNA microarrays studies. A significant proportion of ER? associated gene expression changes was validated by this cross-platform comparison. However, our SAGE study also identified novel sets of genes as highly expressed in ER? (+) invasive breast tumors not previously reported. These observations were further validated in an independent set of human breast tumors by means of real time RT-PCR. Conclusion The integration of the breast cancer comparative transcriptome analysis based on ER? status coupled to the genome-wide identification of high-affinity EREs and GO over-representation analysis, provide useful information for validation and discovery of signaling networks related to estrogen response in this malignancy.

Abba, Martin C; Hu, Yuhui; Sun, Hongxia; Drake, Jeffrey A; Gaddis, Sally; Baggerly, Keith; Sahin, Aysegul; Aldaz, C Marcelo

2005-01-01

72

Including Receptor Flexibility and Induced Fit Effects into the Design of MMP-2 Inhibitors  

PubMed Central

Matrix metalloproteinases (MMPs) comprise a class of flexible proteins required for normal tissue remodeling. Overexpression of MMPs is associated with a wide range of pathophysiological processes, including vascular disease, multiple sclerosis, Alzheimer’s disease, and cancer. Nearly all MMP inhibitors have failed in clinical trials, in part due to lack of specificity. Due to the highly dynamic molecular motions of the MMP-2 binding pockets, the rational drug design of MMP inhibitors has been very challenging. To address these challenges, in the current study we combine computer docking with molecular dynamics (MD) simulations in order to incorporate receptor-flexibility and induced-fit effects into the drug-design process. Our strategy identifies molecular fragments predicted to target multiple MMP-2 binding pockets.

Durrant, Jacob D.; de Oliveira, Cesar Augusto F.; McCammon, J. Andrew

2010-01-01

73

Cannabinoid receptor gene (CNR1): association with IV drug use  

Microsoft Academic Search

The receptors for tetrahydrocannabinol, the active ingredient of marijuana, have been identified. A microsatellite polymorphism (AAT)n at the cannabinoid CB1 (brain) receptor gene (CNR1) consists of 9 alleles. Since the cannabinoid system is part of the reward pathway we examined the hypothesis that genetic variants of the CNR1 gene might be associated with susceptibility to alcohol or drug dependence. The

D E Comings; D Muhleman; R Gade; P Johnson; R Verde; G Saucier; J MacMurray

1997-01-01

74

Aryl hydrocarbon receptor (AhR)-mediated reporter gene expression systems in transgenic tobacco plants  

Microsoft Academic Search

In mammals, the aryl hydrocarbon receptor (AhR) mediates expression of certain genes, including CYP1A1, in response to exposure to dioxins and related compounds. We have constructed a mouse AhR-mediated gene expression systems\\u000a for a ?-glucuronidase (GUS) reporter gene consisting of an AhR, an AhR nuclear translocator (Arnt), and a xenobiotic response element (XRE)-driven promoter\\u000a in transgenic tobacco plants. On treatment

Susumu Kodama; Kumiko Okada; Hideyuki Inui; Hideo Ohkawa

2007-01-01

75

Divergent Evolution among Teleost V1r Receptor Genes  

PubMed Central

The survival of vertebrate species is dependent on the ability of individuals to adequately interact with each other, a function often mediated by the olfactory system. Diverse olfactory receptor repertoires are used by this system to recognize chemicals. Among these receptors, the V1rs, encoded by a very large gene family in most mammals, are able to detect pheromones. Teleosts, which also express V1r receptors, possess a very limited V1r repertoire. Here, taking advantage of the possibility to unequivocally identify V1r orthologs in teleosts, we analyzed the olfactory expression and evolutionary constraints of a pair of clustered fish V1r receptor genes, V1r1 and V1r2. Orthologs of the two genes were found in zebrafish, medaka, and threespine stickleback, but a single representative was observed in tetraodontidae species. Analysis of V1r1 and V1r2 sequences from 12 different euteleost species indicate different evolutionary rates between the two paralogous genes, leading to a highly conserved V1r2 gene and a V1r1 gene under more relaxed selective constraint. Moreover, positively-selected sites were detected in specific branches of the V1r1 clade. Our results suggest a conserved agonist specificity of the V1R2 receptor between euteleost species, its loss in the tetraodontidae lineage, and the acquisition of different chemosensory characteristics for the V1R1 receptor.

Pfister, Patrick; Randall, Jerome; Montoya-Burgos, Juan I.; Rodriguez, Ivan

2007-01-01

76

Cloning and expression of a zebrafish 5-HT(2C) receptor gene.  

PubMed

The 5-HT(2C) receptor is one of 14 different serotonin (5-HT) receptors that control neural function and behavior. Here, we present the entire sequence of a zebrafish 5-HT(2C) receptor cDNA including the 3' untranslated region and the previously unknown 5' untranslated region. The cloned 5-HT(2C) receptor gene is located on chromosome 7, is approximately 202 kbp long, and contains six exons. The coding region of the gene is 1557 bp long and flanked by a 504 bp 5' UTR and a 1474 bp 3' UTR. The deduced protein sequence of 518 amino acids aligns with orthologs of other vertebrates and is 54% identical to the human and mouse 5-HT(2C) receptor protein sequences. The region of the cDNA that encodes the 2nd cytoplasmic loop of the protein shows a 66% identity with vertebrate orthologs and clearly identifies the gene as a 5-HT(2C) receptor gene. Coupling sites for beta-arrestin and calmodulin are conserved in zebrafish. In-situ hybridization shows that the receptor is expressed in the brain and spinal cord including areas such as the olfactory bulb, the dorsal thalamus, the posterior tuberculum, the hypothalamus and the medulla oblongata. Reverse Transcriptase-PCR experiments indicate that the receptor gene can also be active in other tissues such as skin, ovaries, and axial muscle of adult zebrafish. Expression of the 5-HT(2C) receptor during ontogeny was found as early as 2.5 hpf. Five edited adenines in the region of the human, rat and mouse mRNA that encodes the 2nd cytoplasmic loop are conserved in the zebrafish transcript. However, RNA editing was not detected in the zebrafish. The results characterize the zebrafish 5-HT(2C) receptor gene and gene expression pattern for the first time. The similarities to mammalian 5-HT(2C) receptor genes suggest the use of zebrafish for the study of 5-HT(2C) receptor function in behavior, development and drug discovery. PMID:22521866

Schneider, Henning; Fritzky, Luke; Williams, Jesse; Heumann, Christine; Yochum, Marissa; Pattar, Kala; Noppert, Grace; Mock, Vanessa; Hawley, Eric

2012-04-11

77

Selective effects of ligands on vitamin D3 receptor- and retinoid X receptor-mediated gene activation in vivo.  

PubMed Central

Steroid/nuclear hormone receptors are ligand-regulated transcription f factors that play key roles in cell regulation, differentiation, and oncogenesis. Many nuclear receptors, including the human 1,25-dihydroxyvitamin D3 receptor (VDR), bind cooperatively to DNA either as homodimers or as heterodimers with the 9-cis retinoic acid (RA) receptor (retinoid X-receptor [RXR]). We have previously reported that the ligands for VDR and RXR can differentially modulate the affinity of the receptors' interaction with DNA in vitro, primarily by modulating the dimerization status of these receptors. These experiments suggested a complex interaction between VDR and RXR and their respective ligands on inducible target genes in vivo. To examine these effects in cells, we used a transient-transfection strategy whereby we simultaneously introduced two different reporter plasmids that are selectively inducible by each ligand. Although VDR can bind as a homodimer to the osteopontin gene vitamin D response element, we find that a RXR-VDR heterodimer must be the transactivating species from the element in vivo, since RXR enhances and 9-cis RA and other RXR-specific ligands attenuate this induction. Conversely, when VDR is overexpressed, vitamin D3 attenuates 9-cis RA induction from an RXR-responsive element. These effects, however, appear to be very sensitive to both the relative ratios of the two receptors and their respective target elements. Functional RXR-VDR complexes are strictly dependent on the DNA-binding polarity. Chimeric versions of VDR and RXR were also constructed to examine the putative activities of homodimeric receptors; a VDR chimera can transactivate in the absence of RXR, demonstrating that VDR has intrinsic transactivation properties. Taken together, these results establish a complex, sensitive cross talk in vivo between two ligands and their receptors that signal through two distinct endocrine pathways.

Lemon, B D; Freedman, L P

1996-01-01

78

Dopamine D4 Receptor Gene: Novelty or Nonsense?  

Microsoft Academic Search

Although the role of genetics in personality has been studied extensively at a phenomenological level, only lately has the investigation of specific genes been performed. Recent reports suggest that DNA variants of the dopamine D4 receptor gene (DRD4) are associated with the personality trait of novelty seeking; however, others fail to replicate this finding. Such conflicting results suggest either a

Andrew D Paterson; Glen A Sunohara; James L Kennedy

1999-01-01

79

Leptin, leptin gene and leptin receptor gene polymorphism in heart failure with preserved ejection fraction  

Microsoft Academic Search

Heart failure with a normal ejection fraction (HFNEF) is common in obesity and coronary artery disease (CAD). Both ischemia\\u000a and reperfusion induce leptin (LEP) and leptin receptor (LEPR) gene expression. We aimed to investigate the possible associations\\u000a of serum leptin, leptin gene and leptin receptor gene polymorphism with HFNEF in patients with CAD. 100 Egyptian CAD patients\\u000a with HFNEF and

Tarek A. Abd El-Aziz; Randa H. Mohamed; Rasha H. Mohamed; Heba F. Pasha

80

Prolactin receptor and signal transduction to milk protein genes  

SciTech Connect

After cloning of the mammary gland prolactin (PRL) receptor cDNA, a functional assay was established using co-transfection of PRL receptor cDNA together with a milk protein promoter/chloramphenicol acetyl transferase (CAT) construct in Chinese hamster ovary (CHO) cells. Different mutants of the PRL receptor were tested in this CAT assay to delimit the domains in the receptor necessary for signal transduction to milk protein genes. In CHO cells stably transfected with PRL receptor cDNA, high numbers of PRL receptor are expressed. By metabolic labeling and immunoprecipitation, expressed PRL receptor was identified as a single species of 100 kDa. Using these cells, we analyzed the effects of PRL on intracellular free Ca{sup ++} concentration. PRL stimulates Ca{sup ++} entry and induces secondary Ca{sup ++} mobilization. The entry of Ca{sup ++} is a result of an increase in K{sup +} conductance that hyperpolarizes the membranes. We have also analyzed tyrosine phosphorylation induced by PRL. In CHO cells stably transfected with PRL receptor cDNA, PRL induced a very rapid and transient tyrosine phosphorylation of a 100-kDa protein which is most probably the PRL receptor. The same finding was obtained in mammary membranes after PRL injection to lactating rabbits. Whereas tyrosine kinase inhibitors genistein and lavendustin were without effect, PRL stimulation of milk protein gene promoters was partially inhibited by 2 {mu}M herbimycin in CHO cells co-transfected with PRL receptor cDNA and the {Beta} lactoglobulin CAT construct. Taken together these observations indicate that the cytoplasmic domain of the PRL receptor interacts with one or several tyrosine kinases, which may represent early postreceptor events necessary for PRL signal transduction to milk protein genes. 14 refs., 4 figs.

Djiane, J.; Daniel, N.; Bignon, C. [Unite d`Endocrinologie Moleculaire, Jouy en Josas (France)] [and others

1994-06-01

81

Neuropeptide Y receptor gene y6: multiple deaths or resurrections?  

PubMed

The neuropeptide Y family of G-protein-coupled receptors consists of five cloned members in mammals. Four genes give rise to functional receptors in all mammals investigated. The y6 gene is a pseudogene in human and pig and is absent in rat, but generates a functional receptor in rabbit and mouse and probably in the collared peccary (Pecari tajacu), a distant relative of the pig family. We report here that the guinea pig y6 gene has a highly distorted nucleotide sequence with multiple frame-shift mutations. One evolutionary scenario may suggest that y6 was inactivated before the divergence of the mammalian orders and subsequently resurrected in some lineages. However, the pseudogene mutations seem to be distinct in human, pig, and guinea pig, arguing for separate inactivation events. In either case, the y6 gene has a quite unusual evolutionary history with multiple independent deaths or resurrections. PMID:11027673

Starbäck, P; Wraith, A; Eriksson, H; Larhammar, D

2000-10-14

82

Dopamine receptor gene expression by enkephalin neurons in rat forebrain  

SciTech Connect

In situ hybridization experiments were performed with brain sections from normal, control and haloperidol-treated rats to identify and map the cells expressing the D2 dopamine receptor gene. D2 receptor mRNA was detected with radioactive or biotinylated oligonucleotide probes. D2 receptor mRNA was present in glandular cells of the pituitary intermediate lobe and in neurons of the substantia nigra, ventral tegmental area, and forebrain, especially in caudate putamen, nucleus accumbens, olfactory tubercle, and piriform cortex. Hybridization with D2 and preproenkephalin A probes in adjacent sections, as well as combined hybridization with the two probes in the same sections, demonstrated that all detectable enkephalin neurons in the striatum contained the D2 receptor mRNA. Large neurons in caudate putamen, which were unlabeled with the preproenkephalin A probe and which may have been cholinergic, also expressed the D2 receptor gene. Haloperidol treatment (14 or 21 days) provoked an increase in mRNA content for D2 receptor and preproenkephalin A in the striatum. This suggests that the increase in D2 receptor number observed after haloperidol treatment is due to increased activity of the D2 gene. These results indicate that in the striatum, the enkephalin neurons are direct targets for dopamine liberated from mesostriatal neurons.

Le Moine, C.; Normand, E.; Guitteny, A.F.; Fouque, B.; Teoule, R.; Bloch, B. (Universite de Bordeaux II (France))

1990-01-01

83

Identification of olfactory receptor genes in Atlantic salmon Salmo salar.  

PubMed

It has been hypothesized that salmonids use olfactory cues to return to their natal rivers and streams. The key components of the molecular pathways involved in imprinting and homing, however, are still unknown. Aquatic chemical cues are received through the nares and into the nasal cavity that contains a single olfactory organ, the olfactory rosette. The olfactory rosette contains sensory neurons, each of which is thought to express only one olfactory receptor. If odorants are involved in salmonid homing migration then olfactory receptors should play a critical role in the dissipation of information from the environment to the fish. Therefore, to understand the molecular basis for imprinting and homing in Atlantic salmon Salmo salar it is important to identify and characterize the repertoire of olfactory receptors in this species. The first public assembly of the S. salar genome was searched for genes encoding three of the superfamilies of fish olfactory receptors: V2R-like (olfc), V1R-like (ora) and main olfactory receptor (mor). A further six ora genes were added to ora1 and ora2, which had been described previously. In addition, 48 putative mors were identified, 24 of which appear to be functional based on their gene structures and predicted amino-acid sequences. Phylogenetic analyses were then used to compare these S. salar olfactory receptor genes with those of zebrafish Danio rerio, two pufferfish species Takifugu rubripes and Tetraodon nigroviridis, medaka Oryzias latipes and three-spined stickleback Gasterosteus aculeatus. PMID:22803724

Johnstone, K A; Lubieniecki, K P; Koop, B F; Davidson, W S

2012-07-01

84

Melanocortin 3 receptor gene and melanocortin 4 receptor gene mutations: the Asian Perspective.  

PubMed

Melanocortin 4 receptor (MC4R) deficiency resulting from disruption of one or both MC4R alleles represents the commonest monogenic form of human obesity to date. Human MC4R deficiency was reported to affect 4 and 5.8% of severely obese French and British populations respectively. However, studies elsewhere reported low incidence of MC4R mutations in their obese populations. The significance of MC4R mutations in Asian obese populations has not been adequately examined, though small studies in Japan, China, and Singapore reported few or no pathogenic mutations, suggesting a low prevalence in this part of the world. There were also few common mutations described across populations, suggesting a relative lack of founder effect. The pathogenic role of melanocortin 3 receptor gene (MC3R) mutations in human obesity is not as well described and accepted as MC4R mutations, though it is gradually gaining ground. Two common single nucleotide polymorphisms Thr6Lys and Val81Ile within the coding region were associated with higher body fat and leptin levels in obese children, supported by impaired signaling activity in vitro. There were also reports of missense mutations enriched in obese populations. While MC3R mutations are unlikely to result in an autosomal dominant form of monogenic obesity given the lack of strong co-segregation in family studies, the studies so far provided evidence that MC3R can be one of the genes which contributes to increased adiposity, and exert an effect on the human phenotype. PMID:23280863

Lee, Yung Seng

2012-12-01

85

The Emerging Role of the MORF/MRG Gene Family in Various Biological Processes Including Aging  

PubMed Central

Cellular senescence is the dominant phenotype over immortality. In our studies to identify senescence related genes we cloned Morf4 that induced senescence in a subset of tumor cells. Morf4 is a member of a family of 7 genes, and the Morf related genes (Mrg) on chromosomes 15 (Mrg15) and X (MrgX) are also expressed. In contrast to MORF4, MRG15 and MRGX are positive regulators of cell division. All three proteins interact with histone acetylases (HATs) and acetyltransferase (HDACs), suggesting they function in regulation of chromatin dynamics. Mrg15 knockout mice are embryonic lethal, and MEFs derived from Mrg15 null embryos proliferate poorly, enter senescence rapidly and have impaired DNA repair compared to wild type. Mrg15 null embryonic neural stem/progenitor cells also have a decreased capacity for proliferation and differentiation. Further studies are needed to determine the function of this gene family in various biological processes including neural stem/progenitor cell aging.

Chen, Meizhen; Tominaga, Kaoru; Pereira-Smith, Olivia M.

2010-01-01

86

Thrombin modulates the expression of a set of genes including thrombospondin-1 in human microvascular endothelial cells.  

PubMed

Thrombospondin-1 (THBS1) is a large extracellular matrix glycoprotein that affects vasculature systems such as platelet activation, angiogenesis, and wound healing. Increases in THBS1 expression have been liked to disease states including tumor progression, atherosclerosis, and arthritis. The present study focuses on the effects of thrombin activation of the G-protein-coupled, protease-activated receptor-1 (PAR-1) on THBS1 gene expression in the microvascular endothelium. Thrombin-induced changes in gene expression were characterized by microarray analysis of approximately 11,000 different human genes in human microvascular endothelial cells (HMEC-1). Thrombin induced the expression of a set of at least 65 genes including THBS1. Changes in THBS1 mRNA correlated with an increase in the extracellular THBS1 protein concentration. The PAR-1-specific agonist peptide (TFLLRNK-PDK) mimicked thrombin stimulation of THBS1 expression, suggesting that thrombin signaling is through PAR-1. Further studies showed THBS1 expression was sensitive to pertussis toxin and protein kinase C inhibition indicating G(i/o)- and G(q)-mediated pathways. THBS1 up-regulation was also confirmed in human umbilical vein endothelial cells stimulated with thrombin. Analysis of the promoter region of THBS1 and other genes of similar expression profile identified from the microarray predicted an EBOX/EGRF transcription model. Expression of members of each family, MYC and EGR1, respectively, correlated with THBS1 expression. These results suggest thrombin formed at sites of vascular injury increases THBS1 expression into the extracellular matrix via activation of a PAR-1, G(i/o), G(q), EBOX/EGRF-signaling cascade, elucidating regulatory points that may play a role in increased THBS1 expression in disease states. PMID:15817447

McLaughlin, Joseph N; Mazzoni, Maria R; Cleator, John H; Earls, Laurie; Perdigoto, Ana Luisa; Brooks, Joshua D; Muldowney, James A S; Vaughan, Douglas E; Hamm, Heidi E

2005-04-07

87

Odorant receptor genes are expressed in olfactory neuroblastoma.  

PubMed

Olfactory neuroblastoma (ONB) is a malignant tumor found in the human nasal cavity. These tumors are rare and poorly characterized at the molecular level. In this study, we asked whether olfactory-specific genes are expressed in ONBs by using reverse-transcriptase-polymerase chain reaction. We found that the olfactory marker protein and the RIC-8B genes, which are specifically expressed in mature olfactory neurons, are expressed in ONBs. Importantly, we also found that ONBs express a large variety of odorant receptor genes, representative of different odorant receptor gene subfamilies. Our results show that the ONBs express genes that are normally expressed in mature olfactory neurons and indicate that they are derived from progenitor or immature cells in the olfactory epithelium and not from a clonal expansion of a single or few mature olfactory neurons. PMID:24065686

Gonzalez-Kristeller, D C; Gutiyama, L M; Campos, A H; Soares, F A; Brentani, H; Malnic, B

2013-09-10

88

ALK1 signalling analysis identifies angiogenesis related genes and reveals disparity between TGF-? and constitutively active receptor induced gene expression  

PubMed Central

Background TGF-?1 is an important angiogenic factor involved in the different aspects of angiogenesis and vessel maintenance. TGF-? signalling is mediated by the T?RII/ALK5 receptor complex activating the Smad2/Smad3 pathway. In endothelial cells TGF-? utilizes a second type I receptor, ALK1, activating the Smad1/Smad5 pathway. Consequently, a perturbance of ALK1, ALK5 or T?RII activity leads to vascular defects. Mutations in ALK1 cause the vascular disorder hereditary hemorrhagic telangiectasia (HHT). Methods The identification of ALK1 and not ALK5 regulated genes in endothelial cells, might help to better understand the development of HHT. Therefore, the human microvascular endothelial cell line HMEC-1 was infected with a recombinant constitutively active ALK1 adenovirus, and gene expression was studied by using gene arrays and quantitative real-time PCR analysis. Results After 24 hours, 34 genes were identified to be up-regulated by ALK1 signalling. Analysing ALK1 regulated gene expression after 4 hours revealed 13 genes to be up- and 2 to be down-regulated. Several of these genes, including IL-8, ET-1, ID1, HPTP? and TEAD4 are reported to be involved in angiogenesis. Evaluation of ALK1 regulated gene expression in different human endothelial cell types was not in complete agreement. Further on, disparity between constitutively active ALK1 and TGF-?1 induced gene expression in HMEC-1 cells and primary HUVECs was observed. Conclusion Gene array analysis identified 49 genes to be regulated by ALK1 signalling and at least 14 genes are reported to be involved in angiogenesis. There was substantial agreement between the gene array and quantitative real-time PCR data. The angiogenesis related genes might be potential HHT modifier genes. In addition, the results suggest endothelial cell type specific ALK1 and TGF-? signalling.

Lux, Andreas; Salway, Fiona; Dressman, Holly K; Kroner-Lux, Gabriele; Hafner, Mathias; Day, Philip JR; Marchuk, Douglas A; Garland, John

2006-01-01

89

The complex NOD-like receptor repertoire of the coral Acropora digitifera includes novel domain combinations.  

PubMed

Innate immunity in corals is of special interest not only in the context of self-defense but also in relation to the establishment and collapse of their obligate symbiosis with dinoflagellates of the genus Symbiodinium. In innate immunity system of vertebrates, approximately 20 tripartite nucleotide oligomerization domain (NOD)-like receptor proteins that are defined by the presence of a NAIP, CIIA, HET-E and TP1 (NACHT) domain, a C-terminal leucine-rich repeat (LRR) domain, and one of three types of N-terminal effector domain, are known to function as the primary intracellular pattern recognition molecules. Surveying the coral genome revealed not only a larger number of NACHT- and related domain nucleotide-binding adaptor shared by APAF-1, R proteins, and CED-4 (NB-ARC)-encoding loci (~500) than in other metazoans but also surprising diversity of domain combinations among the coral NACHT/NB-ARC-containing proteins; N-terminal effector domains included the apoptosis-related domains caspase recruitment domain (CARD), death effector domain (DED), and Death, and C-terminal repeat domains included LRRs, tetratricopeptide repeats, ankyrin repeats, and WD40 repeats. Many of the predicted coral proteins that contain a NACHT/NB-ARC domain also contain a glycosyl transferase group 1 domain, a novel domain combination first found in metazoans. Phylogenetic analyses suggest that the NACHT/NB-ARC domain inventories of various metazoan lineages, including corals, are largely products of lineage-specific expansions. Many of the NACHT/NB-ARC loci are organized in pairs or triplets in the Acropora genome, suggesting that the large coral NACHT/NB-ARC repertoire has been generated at least in part by tandem duplication. In addition, shuffling of N-terminal effector domains may have occurred after expansions of specific NACHT/NB-ARC-repeat domain types. These results illustrate the extraordinary complexity of the innate immune repertoire of corals, which may in part reflect adaptive evolution to a symbiotic lifestyle in a uniquely complex and challenging environment. PMID:22936719

Hamada, Mayuko; Shoguchi, Eiichi; Shinzato, Chuya; Kawashima, Takeshi; Miller, David J; Satoh, Nori

2012-08-30

90

Variation of the melanocortin 1 receptor gene in the macaques.  

PubMed

Melanocortin 1 receptor (MC1R), a G-coupled seven-transmembrane receptor protein, plays a key role in the regulation of melanin synthesis in mammals. Sequence variation of the MC1R gene (MC1R) has been associated with pigmentation phenotypes in humans and in several animal species. The macaques (genus Macaca) are known to show a marked inter-specific variation in coat color although the causative genetic variation remains unclear. We investigated nucleotide sequences of the MC1R in 67 individuals of 18 macaque species with different coat color phenotypes including black and agouti. Twenty-eight amino acid replacements were identified in the macaques, but none of these amino acid replacements could explain the black coat color of Macaca silenus and the Sulawesi macaque species. Our molecular evolutionary analysis has revealed that nonsynonymous substitution/synonymous substitution (dN/dS) ratio of the MC1R has not been uniform in the macaque groups and, moreover, their coat color and dN/dS ratio were not related. These results suggest that the MC1R is unlikely to be responsible for the coat color variation of the macaques and functions of MC1R other than pigmentation might be associated with the different selective pressures on the MC1R in macaques. PMID:18454455

Nakayama, Kazuhiro; Shotake, Takayoshi; Takeneka, Osamu; Ishida, Takafumi

2008-08-01

91

The neu Gene: An erbB-Homologous Gene Distinct from and Unlinked to the Gene Encoding the EGF Receptor  

Microsoft Academic Search

The neu oncogene, identified in ethylnitrosourea-induced rat neuroglio-blastomas, had strong homology with the erbB gene that encodes the epidermal growth factor receptor. This homology was limited to the region of erbB encoding the tyrosine kinase domain. It was concluded that the neu gene is a distinct novel gene, as it is not coamplified with sequences encoding the EGF receptor in

Alan L. Schechter; Mien-Chie Hung; Lalitha Vaidyanathan; Robert A. Weinberg; Teresa L. Yang-Feng; Uta Francke; Axel Ullrich; Lisa Coussens

1985-01-01

92

Integrated olfactory receptor and microarray gene expression databases  

PubMed Central

Background Gene expression patterns of olfactory receptors (ORs) are an important component of the signal encoding mechanism in the olfactory system since they determine the interactions between odorant ligands and sensory neurons. We have developed the Olfactory Receptor Microarray Database (ORMD) to house OR gene expression data. ORMD is integrated with the Olfactory Receptor Database (ORDB), which is a key repository of OR gene information. Both databases aim to aid experimental research related to olfaction. Description ORMD is a Web-accessible database that provides a secure data repository for OR microarray experiments. It contains both publicly available and private data; accessing the latter requires authenticated login. The ORMD is designed to allow users to not only deposit gene expression data but also manage their projects/experiments. For example, contributors can choose whether to make their datasets public. For each experiment, users can download the raw data files and view and export the gene expression data. For each OR gene being probed in a microarray experiment, a hyperlink to that gene in ORDB provides access to genomic and proteomic information related to the corresponding olfactory receptor. Individual ORs archived in ORDB are also linked to ORMD, allowing users access to the related microarray gene expression data. Conclusion ORMD serves as a data repository and project management system. It facilitates the study of microarray experiments of gene expression in the olfactory system. In conjunction with ORDB, ORMD integrates gene expression data with the genomic and functional data of ORs, and is thus a useful resource for both olfactory researchers and the public.

Liu, Nian; Crasto, Chiquito J; Ma, Minghong

2007-01-01

93

Comparative Genomics of Natural Killer Cell Receptor Gene Clusters  

Microsoft Academic Search

Many receptors on natural killer (NK) cells recognize major histocompatibility complex class I molecules in order to monitor unhealthy tissues, such as cells infected with viruses, and some tumors. Genes encoding families of NK receptors and related sequences are organized into two main clusters in humans: the natural killer complex on Chromosome 12p13.1, which encodes C-type lectin molecules, and the

James Kelley; Lutz Walter; John Trowsdale

2005-01-01

94

A 1-adenosine receptor gene expression in fetal rat brain  

Microsoft Academic Search

Adenosine influences neurotransmitter release, neuronal excitability, and firing rate, through A1-adenosine receptors (A1-R). Caffeine and related methylxanthines are adenosine receptor antagonists. Exposure of developing rodents to caffeine is associated with subtle, long-term changes in neurochemistry and behavior. The developmental appearance of A1-R gene expression was examined in rats by in situ hybridization. On gestational day (GD) 10, A1-R mRNA was

1996-01-01

95

Vascular-protective effects of high-density lipoprotein include the downregulation of the angiotensin II type 1 receptor.  

PubMed

There is growing evidence that a cross-talk exists between the renin-angiotensin (Ang) system and lipoproteins. We investigated the role of high-density lipoprotein (HDL) on Ang II type 1 receptor (AT1R) regulation and subsequent Ang II-mediated signaling under diabetic conditions. To investigate the effect of HDL on AT1R expression in vivo, apolipoprotein A-I gene transfer was performed 5 days after streptozotocin injection. Six weeks after apolipoprotein A-I gene transfer, the 1.9-fold (P=0.001) increase of HDL cholesterol was associated with a 4.7-fold (P<0.05) reduction in diabetes mellitus-induced aortic AT1R expression. Concomitantly, NAD(P)H oxidase activity, Nox 4, and p22(phox) mRNA expression were reduced 2.6-fold, 2.0-fold, and 1.5-fold (P<0.05), respectively, whereas endothelial NO synthase dimerization was increased 3.3-fold (P<0.005). Apolipoprotein A-I transfer improved NO bioavailability as indicated by ameliorated acetylcholine-dependent vasodilation in the streptozotocin-Ad.hapoA-I group compared with streptozotocin-induced diabetes mellitus. In vitro, HDL reduced the hyperglycemia-induced upregulation of the AT1R in human aortic endothelial cells. This was associated with a 1.3-fold and 2.2-fold decreases in reactive oxygen species and NAD(P)H oxidase activity, respectively (P<0.05). Finally, HDL reduced the responsiveness to Ang II, as indicated by decreased oxidative stress in the hyperglycemia+HDL+Ang II group compared with the hyperglycemia+Ang II group. In conclusion, vascular-protective effects of HDL include the downregulation of the AT1R. PMID:19273745

Van Linthout, Sophie; Spillmann, Frank; Lorenz, Mario; Meloni, Marco; Jacobs, Frank; Egorova, Marina; Stangl, Verena; De Geest, Bart; Schultheiss, Heinz-Peter; Tschöpe, Carsten

2009-03-09

96

Chromosomal localization of the human prostanoid receptor gene family  

SciTech Connect

Prostaglandins (PGD{sub 2}, PGE{sub 2}, PGF{sub 2{alpha}}, and PGI{sub 2}) and thromboxane A{sub 2} (TXA{sub 2}) are biologically active molecules derived from the metabolism of arachidonic acid by cyclooxygenases. They produce a wide variety of physiological and pathophysiological effects mediated through specific G protein-coupled cell surface receptors. In this study, we have mapped the chromosomal positions of the human genes that encode the PGE{sub 2} receptor subtypes (PTGER1, PTGER2, and PTGER3), the PGF{sub 2{alpha}} receptor (PTGFR), the PGI{sub 2} receptor (PTGIR), and the TXA{sub 2} receptor (TBXA2R) using in situ hybridization. The PTGER1, TBXA2R, and PTGIR genes mapped to chromosome 19 at positions 19p13.1, 19p13.3, and 19q13.3, respectively. The PTGFR and PTGER3 genes mapped to chromosome 1 at positions 1p31.1 and 1p31.2, respectively, and PTGER2 gene mapped to chromosome band 5p13.1. 16 refs., 1 tab.

Duncan, A.M.V.; Anderson, L.L. [Queen`s Univ., Kingston, Ontario (Canada); Funk, C.D. [Vanderbilt Univ., Nashville, TN (United States)] [and others

1995-02-10

97

A 10-megabase physical map of human Xp21, including the Duchenne muscular dystrophy gene.  

PubMed

Using pulsed-field gel electrophoresis and 12 Xp21-derived DNA probes, we have constructed a continuous restriction map spanning more than 4 million base pairs (4 Mbp), including the Duchenne muscular dystrophy gene of more than 2 Mbp. This detailed map is part of a less detailed map spanning 10 Mbp, also spanning the genes for glycerol kinase and congenital adrenal hypoplasia, constructed under electrophoresis conditions which separated DNA fragments in the range 200 to 4000 kbp. DNA from three different tissues was analyzed, and differential methylation was observed. PMID:3397058

Burmeister, M; Monaco, A P; Gillard, E F; van Ommen, G J; Affara, N A; Ferguson-Smith, M A; Kunkel, L M; Lehrach, H

1988-04-01

98

Linkage map of Cucumis melo including phenotypic traits and sequence-characterized genes.  

PubMed

A new linkage map of Cucumis melo, derived from the F2 progeny of a cross between PI 414723 and C. melo 'TopMark' is presented. The map spans a total of 1421 cM and includes 179 points consisting of random amplified polymorphic DNA (RAPD), amplified fragment length polymorphism (AFLP), inter-simple sequence repeats (ISSRs), simple sequence repeats (SSRs), and restriction fragment length polymorphism (RFLP) markers. The map also includes an aphid resistance trait (Vat) and the sex type gene, andromonoecious (a), the two of which are important in resistance breeding and the control of hybrid seed production, as well as a seed-color gene, Wt-2. Most RFLPs represent sequence-characterized cDNA probes from C. melo and Cucumis sativus. These include resistance gene homologues and genes involved in various aspects of plant development and metabolism. A sub-set of our SSR and RFLP markers were also mapped, as part of this study, on additional mapping populations that were published for this species. This provides important reference points ("anchors"), enabling us to identify several linkage groups with respect to other melon maps. PMID:14608393

Silberstein, Leah; Kovalski, Irina; Brotman, Yariv; Perin, Christophe; Dogimont, Catherine; Pitrat, Michel; Klingler, John; Thompson, Gary; Portnoy, Vitali; Katzir, Nurit; Perl-Treves, Rafael

2003-10-01

99

derived growth factor ? -receptor gene predispose to human neural tube defects  

Microsoft Academic Search

Neural tube defects (NTDs), including anencephaly and spina bifida, are multifactorial diseases that occur with an incidence of 1 in 300 births in the United Kingdom 1 . Mouse models have indicated that deregulated expression of the gene encoding the platelet-derived growth factor ? -receptor (Pdgfra) causes congenital NTDs (refs. 2-4), whereas mutant forms of Pax-1 that have been associated

Paul H. L. J. Joosten; Mascha Toepoel; Edwin C. M. Mariman; J. J. Van Zoelen

100

The collection of NFATc1-dependent transcripts in the osteoclast includes numerous genes non-essential to physiologic bone resorption  

PubMed Central

Osteoclasts are specialized secretory cells of the myeloid lineage important for normal skeletal homeostasis as well as pathologic conditions of bone including osteoporosis, inflammatory arthritis and cancer metastasis. Differentiation of these multinucleated giant cells from precursors is controlled by the cytokine RANKL, which through its receptor RANK initiates a signaling cascade culminating in the activation of transcriptional regulators which induce the expression of the bone degradation machinery. The transcription factor nuclear factor of activated T-cells c1 (NFATc1) is the master regulator of this process and in its absence osteoclast differentiation is aborted both in vitro and in vivo. Differential mRNA expression analysis by microarray is used to identify genes of potential physiologic relevance across nearly all biologic systems. We compared the gene expression profile of murine wild-type and NFATc1-deficient osteoclast precursors stimulated with RANKL and identified that the majority of the known genes important for osteoclastic bone resorption require NFATc1 for induction. Here, five novel RANKL-induced, NFATc1-dependent transcripts in the osteoclast are described: Nhedc2, Rhoc, Serpind1, Adcy3 and Rab38. Despite reasonable hypotheses for the importance of these molecules in the bone resorption pathway and their dramatic induction during differentiation, the analysis of mice with mutations in these genes failed to reveal a function in osteoclast biology. Compared to littermate controls, none of these mutants demonstrated a skeletal phenotype in vivo or alterations in osteoclast differentiation or function in vitro. These data highlight the need for rigorous validation studies to complement expression profiling results before functional importance can be assigned to highly regulated genes in any biologic process.

Charles, Julia F.; Coury, Fabienne; Sulyanto, Rosalyn; Sitara, Despina; Wu, Jing; Brady, Nicholas; Tsang, Kelly; Sigrist, Kirsten; Tollefsen, Douglas M.; He, Li; Storm, Daniel; Aliprantis, Antonios O.

2012-01-01

101

Natural Killer Cell Receptor Genes in the Family Equidae: Not only Ly49  

PubMed Central

Natural killer (NK) cells have important functions in immunity. NK recognition in mammals can be mediated through killer cell immunoglobulin-like receptors (KIR) and/or killer cell lectin-like Ly49 receptors. Genes encoding highly variable NK cell receptors (NKR) represent rapidly evolving genomic regions. No single conservative model of NKR genes was observed in mammals. Single-copy low polymorphic NKR genes present in one mammalian species may expand into highly polymorphic multigene families in other species. In contrast to other non-rodent mammals, multiple Ly49-like genes appear to exist in the horse, while no functional KIR genes were observed in this species. In this study, Ly49 and KIR were sought and their evolution was characterized in the entire family Equidae. Genomic sequences retrieved showed the presence of at least five highly conserved polymorphic Ly49 genes in horses, asses and zebras. These findings confirmed that the expansion of Ly49 occurred in the entire family. Several KIR-like sequences were also identified in the genome of Equids. Besides a previously identified non-functional KIR-Immunoglobulin-like transcript fusion gene (KIR-ILTA) and two putative pseudogenes, a KIR3DL-like sequence was analyzed. In contrast to previous observations made in the horse, the KIR3DL sequence, genomic organization and mRNA expression suggest that all Equids might produce a functional KIR receptor protein molecule with a single non-mutated immune tyrosine-based inhibition motif (ITIM) domain. No evidence for positive selection in the KIR3DL gene was found. Phylogenetic analysis including rhinoceros and tapir genomic DNA and deduced amino acid KIR-related sequences showed differences between families and even between species within the order Perissodactyla. The results suggest that the order Perissodactyla and its family Equidae with expanded Ly49 genes and with a potentially functional KIR gene may represent an interesting model for evolutionary biology of NKR genes.

Futas, Jan; Horin, Petr

2013-01-01

102

Peroxisome Proliferator-Activated Receptor Alpha Target Genes  

PubMed Central

The peroxisome proliferator-activated receptor alpha (PPAR?) is a ligand-activated transcription factor involved in the regulation of a variety of processes, ranging from inflammation and immunity to nutrient metabolism and energy homeostasis. PPAR? serves as a molecular target for hypolipidemic fibrates drugs which bind the receptor with high affinity. Furthermore, PPAR? binds and is activated by numerous fatty acids and fatty acid-derived compounds. PPAR? governs biological processes by altering the expression of a large number of target genes. Accordingly, the specific role of PPAR? is directly related to the biological function of its target genes. Here, we present an overview of the involvement of PPAR? in lipid metabolism and other pathways through a detailed analysis of the different known or putative PPAR? target genes. The emphasis is on gene regulation by PPAR? in liver although many of the results likely apply to other organs and tissues as well.

Rakhshandehroo, Maryam; Knoch, Bianca; Muller, Michael; Kersten, Sander

2010-01-01

103

NK gene complex dynamics and selection for NK cell receptors  

PubMed Central

Natural Killer (NK) cells play important roles in innate defense against infectious agents particularly viruses and also tumors. They mediate their effects through direct cytolysis, release of cytokines and regulation of subsequent adaptive immune responses. NK cells are equipped with sophisticated arrays of inhibitory and activation receptors that regulate their function. In this review we illustrate some of the major evolutionary relationships between NK cell receptors among different animal species and what some of the major mechanisms are that give rise to this diversity in receptor families, including the potential roles of pathogens such as viruses in driving receptor evolution.

Brown, Michael G.; Scalzo, Anthony A.

2008-01-01

104

The Natural History of Class I Primate Alcohol Dehydrogenases Includes Gene Duplication, Gene Loss, and Gene Conversion  

PubMed Central

Background Gene duplication is a source of molecular innovation throughout evolution. However, even with massive amounts of genome sequence data, correlating gene duplication with speciation and other events in natural history can be difficult. This is especially true in its most interesting cases, where rapid and multiple duplications are likely to reflect adaptation to rapidly changing environments and life styles. This may be so for Class I of alcohol dehydrogenases (ADH1s), where multiple duplications occurred in primate lineages in Old and New World monkeys (OWMs and NWMs) and hominoids. Methodology/Principal Findings To build a preferred model for the natural history of ADH1s, we determined the sequences of nine new ADH1 genes, finding for the first time multiple paralogs in various prosimians (lemurs, strepsirhines). Database mining then identified novel ADH1 paralogs in both macaque (an OWM) and marmoset (a NWM). These were used with the previously identified human paralogs to resolve controversies relating to dates of duplication and gene conversion in the ADH1 family. Central to these controversies are differences in the topologies of trees generated from exonic (coding) sequences and intronic sequences. Conclusions/Significance We provide evidence that gene conversions are the primary source of difference, using molecular clock dating of duplications and analyses of microinsertions and deletions (micro-indels). The tree topology inferred from intron sequences appear to more correctly represent the natural history of ADH1s, with the ADH1 paralogs in platyrrhines (NWMs) and catarrhines (OWMs and hominoids) having arisen by duplications shortly predating the divergence of OWMs and NWMs. We also conclude that paralogs in lemurs arose independently. Finally, we identify errors in database interpretation as the source of controversies concerning gene conversion. These analyses provide a model for the natural history of ADH1s that posits four ADH1 paralogs in the ancestor of Catarrhine and Platyrrhine primates, followed by the loss of an ADH1 paralog in the human lineage.

Carrigan, Matthew A.; Uryasev, Oleg; Davis, Ross P.; Zhai, LanMin; Hurley, Thomas D.; Benner, Steven A.

2012-01-01

105

Melanocortin-4 Receptor Gene Polymorphisms in Obese Patients  

Microsoft Academic Search

Obesity is a complex disease caused by both genetics and environmental factors. Melanocortin-4 receptor (MC4R) (MIM 155541) gene polymorphisms were reported to be the cause of monogenic obesity in humans. We studied three polymorphisms\\u000a (Val50Met, Val103Ile, and Ser58Cys) and a mutation (Asn274Ser) of the MC4R gene in 203 obese patients and in 110 healthy subjects in the Turkish population. A

Erkan Yurtcu; Akin Yilmaz; Zubeyde Ozkurt; Emine Kolukisa; Murat Yilmaz; Hatice Keles; Mehmet Ali Ergun; Ilhan Yetkin; Adnan Menevse

2009-01-01

106

Gene-specific patterns of coregulator requirements by estrogen receptor-? in breast cancer cells.  

PubMed

Progesterone receptor (PgR) controls the menstrual cycle, pregnancy, embryonic development, and homeostasis, and it plays important roles in breast cancer development and progression. However, the requirement of coregulators for estrogen-induced expression of the PgR gene has not been fully explored. Here we used RNA interference to demonstrate dramatic differences in requirements of 10 different coregulators for estrogen-regulated expression of six different genes, including PgR and the well-studied TFF1 (or pS2) gene in MCF-7 breast cancer cells. Full estrogen-induced expression of TFF1 required all ten coregulators, but PgR induction required only four of the 10 coregulators. Chromatin immunoprecipitation studies demonstrated several mechanisms responsible for the differential coregulator requirements. Actin-binding coregulator Flightless-I, required for TFF1 expression and recruited to that gene by estrogen receptor-? (ER?), is not required for PgR expression and not recruited to that gene. Protein acetyltransferase tat-interactive protein 60 and ATP-dependent chromatin remodeler Brahma Related Gene 1 are recruited to both genes but are required only for TFF1 expression. Histone methyltransferase G9a is recruited to both genes and required for estrogen-induced expression of TFF1 but negatively regulates estrogen-induced expression of PgR. In contrast, histone methyltransferase myeloid/lymphoid or mixed-lineage leukemia 1 (MLL1), pioneer factor Forkhead box A1, and p160 coregulator steroid receptor coactivator-3 are required for expression of and are recruited to both genes. Depletion of MLL1 decreased ER? binding to the PgR and TFF1 genes. In contrast, depletion of G9a enhanced ER? binding to the PgR gene but had no effect on ER? binding to the TFF1 gene. These studies suggest that differential promoter architecture is responsible for promoter-specific mechanisms of gene regulation. PMID:22543272

Won Jeong, Kwang; Chodankar, Rajas; Purcell, Daniel J; Bittencourt, Danielle; Stallcup, Michael R

2012-04-27

107

Spliceostatin A blocks angiogenesis by inhibiting global gene expression including VEGF.  

PubMed

Spliceostatin A (SSA) is a methylated derivative of an antitumor natural product FR901464, which specifically binds and inhibits the SF3b spliceosome sub-complex. To investigate the selective antitumor activity of SSA, we focused on the regulation of vascular endothelial growth factor (VEGF) mRNA, since VEGF is a key regulatory component in tumor angiogenesis and known for the intricate regulation of mRNA processing, such as alternative splicing. We found that in HeLa cells SSA reduced the amount of both mRNA and protein of VEGF. Spliceostatin A not only inhibited the splicing reaction of VEGF pre-mRNA but also reduced the total amount of VEGF's transcripts, while SSA affected GAPDH mRNA to a lesser extent. Given a significant reduction in VEGF gene expression, SSA was expected to possess anti-angiogenic activity in vivo. Indeed, SSA inhibited cancer cell-derived angiogenesis in vivo in a chicken chorioallantoic membrane (CAM) assay. The inhibition of angiogenesis with SSA was abolished by addition of exogenous VEGF. We also performed global gene expression analyses of HeLa cells and found that the expression levels of 38% of total genes including VEGF decreased to <50% of the basal levels following 16?h of SSA treatment. These results suggest that the global interference of gene expression including VEGF in tumor cells is at least one of the mechanisms by which SSA (or FR901464) exhibits its strong antitumor activity. PMID:20726856

Furumai, Ryohei; Uchida, Kazuyo; Komi, Yusuke; Yoneyama, Misao; Ishigami, Ken; Watanabe, Hidenori; Kojima, Soichi; Yoshida, Minoru

2010-11-01

108

Regulation of dihydropyridine receptor and ryanodine receptor gene expression in regenerating skeletal muscle  

Microsoft Academic Search

One of the the major properties of mature skeletal muscle is its ability to regenerate after injury. The purpose of the present\\u000a study was to determine whether the expression of genes encoding the dihydropyridine receptor calcium channel (DHPR) and the\\u000a ryanodine receptor (RyR), which play a critical role in excitation–contraction coupling, is regulated by skeletal muscle regeneration.\\u000a The process of

Yann Péréon; Javier Navarro; Vincenzo Sorrentino; Jean-Pierre Louboutin; Jacques Noireaud; P. Palade

1996-01-01

109

Mineralocorticoid receptor interaction with SP1 generates a new response element for pathophysiologically relevant gene expression  

PubMed Central

The mineralocorticoid receptor (MR) is a ligand-induced transcription factor belonging to the steroid receptor family and involved in water-electrolyte homeostasis, blood pressure regulation, inflammation and fibrosis in the renocardiovascular system. The MR shares a common hormone-response-element with the glucocorticoid receptor but nevertheless elicits MR-specific effects including enhanced epidermal growth factor receptor (EGFR) expression via unknown mechanisms. The EGFR is a receptor tyrosine kinase that leads to activation of MAP kinases, but that can also function as a signal transducer for other signaling pathways. In the present study, we mechanistically investigate the interaction between a newly discovered MR- but not glucocorticoid receptor- responsive-element (=MRE1) of the EGFR promoter, specificity protein 1 (SP1) and MR to gain general insights into MR-specificity. Biological relevance of the interaction for EGFR expression and consequently for different signaling pathways in general is demonstrated in human, rat and murine vascular smooth muscle cells and cells of EGFR knockout mice. A genome-wide promoter search for identical binding regions followed by quantitative PCR validation suggests that the identified MR-SP1–MRE1 interaction might be applicable to other genes. Overall, a novel principle of MR-specific gene expression is explored that applies to the pathophysiologically relevant expression of the EGFR and potentially also to other genes.

Meinel, Sandra; Ruhs, Stefanie; Schumann, Katja; Stratz, Nicole; Trenkmann, Kay; Schreier, Barbara; Grosse, Ivo; Keilwagen, Jens; Gekle, Michael; Grossmann, Claudia

2013-01-01

110

Mineralocorticoid receptor interaction with SP1 generates a new response element for pathophysiologically relevant gene expression.  

PubMed

The mineralocorticoid receptor (MR) is a ligand-induced transcription factor belonging to the steroid receptor family and involved in water-electrolyte homeostasis, blood pressure regulation, inflammation and fibrosis in the renocardiovascular system. The MR shares a common hormone-response-element with the glucocorticoid receptor but nevertheless elicits MR-specific effects including enhanced epidermal growth factor receptor (EGFR) expression via unknown mechanisms. The EGFR is a receptor tyrosine kinase that leads to activation of MAP kinases, but that can also function as a signal transducer for other signaling pathways. In the present study, we mechanistically investigate the interaction between a newly discovered MR- but not glucocorticoid receptor- responsive-element (=MRE1) of the EGFR promoter, specificity protein 1 (SP1) and MR to gain general insights into MR-specificity. Biological relevance of the interaction for EGFR expression and consequently for different signaling pathways in general is demonstrated in human, rat and murine vascular smooth muscle cells and cells of EGFR knockout mice. A genome-wide promoter search for identical binding regions followed by quantitative PCR validation suggests that the identified MR-SP1-MRE1 interaction might be applicable to other genes. Overall, a novel principle of MR-specific gene expression is explored that applies to the pathophysiologically relevant expression of the EGFR and potentially also to other genes. PMID:23821666

Meinel, Sandra; Ruhs, Stefanie; Schumann, Katja; Strätz, Nicole; Trenkmann, Kay; Schreier, Barbara; Grosse, Ivo; Keilwagen, Jens; Gekle, Michael; Grossmann, Claudia

2013-07-01

111

Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism  

SciTech Connect

The allelic association of the human D2 dopamine receptor gene with the binding characteristics of the D2 dopamine receptor was determined in 66 brains of alcoholic and non-alcoholic subjects. In a blinded experiment, DNA from the cerebral cortex was treated with the restriction endonuclease Taql and probed with a 1.5-kilobase (kb) digest of a clone (lambda hD2G1) of the human D2 dopamine receptor gene. The binding characteristics (Kd (binding affinity) and Bmax (number of binding sites)) of the D2 dopamine receptor were determined in the caudate nuclei of these brains using tritiated spiperone as the ligand. The adjusted Kd was significantly lower in alcoholic than in nonalcoholic subjects. In subjects with the A1 allele, in whom a high association with alcoholism was found, the Bmax was significantly reduced compared with the Bmax of subjects with the A2 allele. Moreover, a progressively reduced Bmax was found in subjects with A2/A2, A1/A2, and A1/A1 alleles, with subjects with A2/A2 having the highest mean values, and subjects with A1/A1, the lowest. The polymorphic pattern of the D2 dopamine receptor gene and its differential expression of receptors suggests the involvement of the dopaminergic system in conferring susceptibility to at least one subtype of severe alcoholism.

Noble, E.P.; Blum, K.; Ritchie, T.; Montgomery, A.; Sheridan, P.J. (Neuropsychiatric Institute, UCLA (USA))

1991-07-01

112

Nonessential Genes of Phage ?YeO3-12 Include Genes Involved in Adaptation to Growth on Yersinia enterocolitica Serotype O:3  

PubMed Central

Bacteriophage ?YeO3-12 is a T7/T3-related lytic phage that naturally infects Yersinia enterocolitica serotype O:3 strains by using the lipopolysaccharide O polysaccharide (O antigen) as its receptor. The phage genome is a 39,600-bp-long linear, double-stranded DNA molecule that contains 58 genes. The roles of many of the genes are currently unknown. To identify nonessential genes, the isolated phage DNA was subjected to MuA transposase-catalyzed in vitro transposon insertion mutagenesis with a lacZ? gene-containing reporter transposon. Following electroporation into Escherichia coli DH10B and subsequent infection of E. coli JM109/pAY100, a strain that expresses the Y. enterocolitica O:3 O antigen on its surface, mutant phage clones were identified by their ?-galactosidase activity, manifested as a blue color on indicator plates. Transposon insertions were mapped in a total of 11 genes located in the early and middle regions of the phage genome. All of the mutants had efficiencies of plating (EOPs) and fitnesses identical to those of the wild-type phage when grown on E. coli JM109/pAY100. However, certain mutants exhibited altered phenotypes when grown on Y. enterocolitica O:3. Transposon insertions in genes 0.3 to 0.7 decreased the EOP on Y. enterocolitica O:3, while the corresponding deletions did not, suggesting that the low EOP was not caused by inactivation of the genes per se. Instead, it was shown that in these mutants the low EOP was due to the delayed expression of gene 1, coding for RNA polymerase. On the other hand, inactivation of gene 1.3 or 3.5 by either transposon insertion or deletion decreased phage fitness when grown on Y. enterocolitica. These results indicate that ?YeO3-12 has adapted to utilize Y. enterocolitica as its host and that these adaptations include the products of genes 1.3 and 3.5, DNA ligase and lysozyme, respectively.

Kiljunen, Saija; Vilen, Heikki; Pajunen, Maria; Savilahti, Harri; Skurnik, Mikael

2005-01-01

113

Individual variation in a cholinergic receptor gene modulates attention  

Microsoft Academic Search

Cholinergic influences on attention are well documented and recent evidence indicates that genetic variation in the ?4?2 nicotinic receptor affects attentional networks of the brain. Several behavioral and electrophysiological studies have shown that a common polymorphism in the CHRNA4 gene (rs1044396) affects aspects of visual and auditory attentional processing. We examined genetic effects on neuropsychological measures of memory and attention

Ivar Reinvang; Astri J. Lundervold; Helge Rootwelt; Eike Wehling; Thomas Espeseth

2009-01-01

114

EGF receptor gene mutations are common in lung cancers from  

Microsoft Academic Search

Somatic mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene are reportedly associated with sensitivity of lung cancers to gefitinib (Iressa), kinase inhibitor. In-frame deletions occur in exon 19, whereas point mutations occur frequently in codon 858 (exon 21). We found from sequencing the EGFR TK domain that 7 of 10 gefitinib-sensitive tumors had

William Pao; Vincent Miller; Maureen Zakowski; Jennifer Doherty; Katerina Politi; Inderpal Sarkaria; Bhuvanesh Singh; Robert Heelan; Valerie Rusch; Lucinda Fulton; Elaine Mardis; Doris Kupfer; Richard Wilson; Mark Kris; Harold Varmus

2004-01-01

115

EXPRESSION OF THE PROGLUCAGON AND COMPANION RECEPTOR GENES IN CHICKENS  

Technology Transfer Automated Retrieval System (TEKTRAN)

Expression of the proglucagon (PG) gene in mammals produces a single mRNA transcript that encodes glucagon and two glucagon-like peptide hormones (GLP-1 and GLP-2). Glucagon, GLP-1 and GLP-2 bind to specific receptors that are expressed in different tissues. These peptide hormones in conjunction wit...

116

Variants in the vitamin D receptor gene and asthma  

Microsoft Academic Search

BACKGROUND: Early lifetime exposure to dietary or supplementary vitamin D has been predicted to be a risk factor for later allergy. Twin studies suggest that response to vitamin D exposure might be influenced by genetic factors. As these effects are primarily mediated through the vitamin D receptor (VDR), single base variants in this gene may be risk factors for asthma

Matthias Wjst; Gruppe Molekulare Epidemiologie

2005-01-01

117

Characterization of the "CCR5" Chemokine Receptor Gene  

ERIC Educational Resources Information Center

|The life cycle of retroviruses is an essential topic of modern cell biology instruction. Furthermore, the process of HIV viral entry into the cell is a question of great interest in basic and clinical biology. This paper describes how students can easily recover their own DNA, amplify a portion of the "CCR5" chemokine receptor gene, characterize…

Thomas, John C.

2004-01-01

118

Genetic polymorphisms in the estrogen receptor beta ( ESR2 ) gene and the risk of epithelial ovarian carcinoma  

Microsoft Academic Search

Ovarian cancer is influenced by exogenous and endogenous estrogens as suggested by experimental and epidemiological evidence.\\u000a Estrogen receptor beta is a predominant estrogen receptor in the normal ovary. Polymorphisms in the estrogen receptor beta\\u000a gene (ESR2) might influence epithelial ovarian risk through regulation of cell proliferation and apoptosis. This population-based case–control\\u000a study included 313 women with epithelial ovarian carcinoma and

Galina Lurie; Lynne R. Wilkens; Pamela J. Thompson; Katharine E. McDuffie; Michael E. Carney; Keith Y. Terada; Marc T. Goodman

2009-01-01

119

Identification of drugs including a dopamine receptor antagonist that selectively target cancer stem cells.  

PubMed

Selective targeting of cancer stem cells (CSCs) offers promise for a new generation of therapeutics. However, assays for both human CSCs and normal stem cells that are amenable to robust biological screens are limited. Using a discovery platform that reveals differences between neoplastic and normal human pluripotent stem cells (hPSC), we identify small molecules from libraries of known compounds that induce differentiation to overcome neoplastic self-renewal. Surprisingly, thioridazine, an antipsychotic drug, selectively targets the neoplastic cells, and impairs human somatic CSCs capable of in vivo leukemic disease initiation while having no effect on normal blood SCs. The drug antagonizes dopamine receptors that are expressed on CSCs and on breast cancer cells as well. These results suggest that dopamine receptors may serve as a biomarker for diverse malignancies, demonstrate the utility of using neoplastic hPSCs for identifying CSC-targeting drugs, and provide support for the use of differentiation as a therapeutic strategy. PMID:22632761

Sachlos, Eleftherios; Risueño, Ruth M; Laronde, Sarah; Shapovalova, Zoya; Lee, Jong-Hee; Russell, Jennifer; Malig, Monika; McNicol, Jamie D; Fiebig-Comyn, Aline; Graham, Monica; Levadoux-Martin, Marilyne; Lee, Jung Bok; Giacomelli, Andrew O; Hassell, John A; Fischer-Russell, Daniela; Trus, Michael R; Foley, Ronan; Leber, Brian; Xenocostas, Anargyros; Brown, Eric D; Collins, Tony J; Bhatia, Mickie

2012-05-24

120

Reciprocal activation of Xenobiotic response genes by nuclear receptors SXR/PXR and CAR  

PubMed Central

The cytochrome P450 (CYP) gene products such as CYP3A and CYP2B are essential for the metabolism of steroid hormones and xenochemicals including prescription drugs. Nuclear receptor SXR/PXR (steroid and xenobiotic receptor/pregnenolone X receptor) has been shown both biochemically and genetically to activate CYP3A genes, while similar studies have established constitutive androstane receptor (CAR) as a CYP2B regulator. The response elements in these genes are also distinct, furthering the concept of independent regulation. Unexpectedly, we found that SXR can regulate CYP2B, both in cultured cells and in transgenic mice via adaptive recognition of the phenobarbital response element (PBRE). In a type of functional symmetry, orphan receptor CAR was also found to activate CYP3A through previously defined SXR/PXR response elements. These observations not only provide a rational explanation for the activation of multiple CYP gene classes by certain xenobiotics, but also reveal the existence of a metabolic safety net that confers a second layer of protection to the harmful effects of toxic compounds and at the same time increases the propensity for drug–drug interactions.

Xie, Wen; Barwick, Joyce L.; Simon, Cynthia M.; Pierce, Alexis M.; Safe, Stephen; Blumberg, Bruce; Guzelian, Philip S.; Evans, Ronald M.

2000-01-01

121

Linkage analysis of schizophrenia with five dopamine receptor genes in nine pedigrees  

PubMed Central

Alterations in dopamine neurotransmission have been strongly implicated in the pathogenesis of schizophrenia for nearly 2 decades. Recently, the genes for five dopamine receptors have been cloned and characterized, and genetic and physical map information has become available. Using these five loci as candidate genes, we have tested for genetic linkage to schizophrenia in nine multigenerational families which include multiple affected individuals. In addition to testing conservative disease models, we have used a neurophysiological indicator variable, the P50 auditory evoked response. Deficits in gating of the P50 response have been shown to segregate with schizophrenia in this sample and may identify carriers of gene(s) predisposing for schizophrenia. Linkage results were consistently negative, indicating that a defect at any of the actual receptor sites is unlikely to be a major contributor to schizophrenia in the nine families studied.

Coon, Hilary; Byerley, William; Holik, John; Hoff, Mark; Myles-Worsley, Marina; Lannfelt, Lars; Sokoloff, Pierre; Schwartz, Jean-Charles; Waldo, Merilyne; Freedman, Robert; Plaetke, Rosemarie

1993-01-01

122

The melanocortin-1-receptor gene is the major freckle gene  

Microsoft Academic Search

strict definitions. The entire coding sequence of the MC1R gene was analyzed by single-strand conform- ation polymorphism analysis followed by sequence analyses. Carriers of one or two MC1R gene variants had a 3- and 11-fold increased risk of developing ephelides, respectively (both P < 0.0001), whereas the risk of developing severe solar lentigines was increased 1.5- and 2-fold (P =

Maarten Bastiaens; Nelleke Gruis; Wilma Bergman; Rudi Westendorp; Bert-Jan Vermeer; Jan-Nico Bouwes Bavinck

2001-01-01

123

Leptin Gene and Leptin Receptor Gene Polymorphisms Are Associated with Sweet Preference and Obesity  

Microsoft Academic Search

Leptin is an adipocyte-secreted hormone that regulates food intake and body weight, and that was recently reported to suppress sweet sensitivity in an animal model. We investigated the associations among sweet preference, obesity, and polymorphisms of the leptin gene (LEP) or leptin receptor gene (LEPR). A total of 3,653 residents randomly selected from among the citizens of Suita City, Osaka,

Einosuke Mizuta; Yoshihiro Kokubo; Itaru Yamanaka; Yoshihiro Miyamoto; Akira Okayama; Yasunao Yoshimasa; Hitonobu Tomoike; Hiroko Morisaki; Takayuki Morisaki

2008-01-01

124

Identification of chemosensory receptor genes in Manduca sexta and knockdown by RNA interference  

PubMed Central

Background Insects detect environmental chemicals via a large and rapidly evolving family of chemosensory receptor proteins. Although our understanding of the molecular genetic basis for Drosophila chemoreception has increased enormously in the last decade, similar understanding in other insects remains limited. The tobacco hornworm, Manduca sexta, has long been an important model for insect chemosensation, particularly from ecological, behavioral, and physiological standpoints. It is also a major agricultural pest on solanaceous crops. However, little sequence information and lack of genetic tools has prevented molecular genetic analysis in this species. The ability to connect molecular genetic mechanisms, including potential lineage-specific changes in chemosensory genes, to ecologically relevant behaviors and specializations in M. sexta would be greatly beneficial. Results Here, we sequenced transcriptomes from adult and larval chemosensory tissues and identified chemosensory genes based on sequence homology. We also used dsRNA feeding as a method to induce RNA interference in larval chemosensory tissues. Conclusions We report identification of new chemosensory receptor genes including 17 novel odorant receptors and one novel gustatory receptor. Further, we demonstrate that systemic RNA interference can be used in larval olfactory neurons to reduce expression of chemosensory receptor transcripts. Together, our results further the development of M. sexta as a model for functional analysis of insect chemosensation.

2012-01-01

125

Human Immunodeficiency Virus Type 1Induced Macrophage Gene Expression Includes the p21 Gene, a Target for Viral Regulation  

Microsoft Academic Search

In contrast to CD4 T cells, human immunodeficiency virus type 1 (HIV-1)-infected macrophages typically resist cell death, support viral replication, and consequently, may facilitate HIV-1 transmission. To elucidate how the virus commandeers the macrophage's intracellular machinery for its benefit, we analyzed HIV-1-in- fected human macrophages for virus-induced gene transcription by using multiple parameters, including cDNA expression arrays. HIV-1 infection induced

Nancy Vazquez; Teresa Greenwell-Wild; Nancy J. Marinos; William D. Swaim; Salvador Nares; David E. Ott; Ulrich Schubert; Peter Henklein; Jan M. Orenstein; M. B. Sporn; S. M. Wahl

2005-01-01

126

Gene expression profiles of estrogen receptor positive and estrogen receptor negative breast cancers are detectable in histologically normal breast epithelium  

PubMed Central

Purpose Previously, we found that gene expression in histologically normal breast epithelium (NlEpi) from women at high breast cancer risk can resemble gene expression in NlEpi from cancer-containing breasts. Therefore, we hypothesized that gene expression characteristic of a cancer subtype might be seen in NlEpi of breasts containing that subtype. Experimental Design We examined gene expression in 46 cases of microdissected NlEpi from untreated women undergoing breast cancer surgery. From 30 age-matched cases (15 estrogen receptor (ER)+, 15 ER-) we used Affymetryix U133A arrays. From 16 independent cases (9 ER+, 7 ER-), we validated selected genes using qPCR. We then compared gene expression between NlEpi and invasive breast cancer using 4 publicly available datasets. Results We identified 198 genes that are differentially expressed between NlEpi from breasts with ER+ (NlEpiER+) compared to ER- cancers (NlEpiER-). These include genes characteristic of ER+ and ER- cancers (e.g., ESR1, GATA3, and CX3CL1, FABP7). QPCR validated the microarray results in both the 30 original cases and the 16 independent cases. Gene expression in NlEpiER+ and NlEpiER- resembled gene expression in ER+ and ER- cancers, respectively: 25-53% of the genes or probes examined in 4 external datasets overlapped between NlEpi and the corresponding cancer subtype. Conclusions Gene expression differs in NlEpi of breasts containing ER+ compared to ER- breast cancers. These differences echo differences in ER+ and ER- invasive cancers. NlEpi gene expression may help elucidate subtype-specific risk signatures, identify early genomic events in cancer development and locate targets for prevention and therapy.

Graham, Kelly; Ge, Xijin; de las Morenas, Antonio; Tripathi, Anusri; Rosenberg, Carol L.

2010-01-01

127

The nuclear receptors pregnane X receptor and constitutive androstane receptor contribute to the impact of fipronil on hepatic gene expression linked to thyroid hormone metabolism.  

PubMed

Fipronil is described as a thyroid disruptor in rat. Based on the hypothesis that this results from a perturbation of hepatic thyroid hormone metabolism, our goal was to investigate the pathways involved in fipronil-induced liver gene expression regulations. First, we performed a microarray screening in the liver of rats treated with fipronil or vehicle. Fipronil treatment led to the upregulation of several genes involved in the metabolism of xenobiotics, including the cytochrome P450 Cyp2b1, Cyp2b2 and Cyp3a1, the carboxylesterases Ces2 and Ces6, the phase II enzymes Ugt1a1, Sult1b1 and Gsta2, and the membrane transporters Abcc2, Abcc3, Abcg5, Abcg8, Slco1a1 and Slco1a4. Based on a large overlap with the target genes of constitutive androstane receptor (CAR) and pregnane X receptor (PXR), we postulated that these two nuclear receptors are involved in mediating the effects of fipronil on liver gene expression in rodents. We controlled that liver gene expression changes induced by fipronil were generally reproduced in mice, and then studied the effects of fipronil in wild-type, CAR- and PXR-deficient mice. For most of the genes studied, the gene expression modulations were abolished in the liver of PXR-deficient mice and were reduced in the liver of CAR-deficient mice. However, CAR and PXR activation in mouse liver was not associated with a marked increase of thyroid hormone clearance, as observed in rat. Nevertheless, our data clearly indicate that PXR and CAR are key modulators of the hepatic gene expression profile following fipronil treatment which, in rats, may contribute to increase thyroid hormone clearance. PMID:23962444

Roques, Béatrice B; Leghait, Julien; Lacroix, Marlène Z; Lasserre, Frédéric; Pineau, Thierry; Viguié, Catherine; Martin, Pascal G P

2013-08-17

128

Identification of significant association and gene-gene interaction of GABA receptor subunit genes in autism.  

PubMed

Autism is a common neurodevelopmental disorder with a significant genetic component. Existing research suggests that multiple genes contribute to autism and that epigenetic effects or gene-gene interactions are likely contributors to autism risk. However, these effects have not yet been identified. Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the adult brain, has been implicated in autism etiology. Fourteen known autosomal GABA receptor subunit genes were studied to look for the genes associated with autism and their possible interactions. Single-nucleotide polymorphisms (SNPs) were screened in the following genes: GABRG1, GABRA2, GABRA4, and GABRB1 on chromosome 4p12; GABRB2, GABRA6, GABRA1, GABRG2, and GABRP on 5q34-q35.1; GABRR1 and GABRR2 on 6q15; and GABRA5, GABRB3, and GABRG3 on 15q12. Intronic and/or silent mutation SNPs within each gene were analyzed in 470 white families with autism. Initially, SNPs were used in a family-based study for allelic association analysis--with the pedigree disequilibrium test and the family-based association test--and for genotypic and haplotypic association analysis--with the genotype-pedigree disequilibrium test (geno-PDT), the association in the presence of linkage (APL) test, and the haplotype family-based association test. Next, with the use of five refined independent marker sets, extended multifactor-dimensionality reduction (EMDR) analysis was employed to identify the models with locus joint effects, and interaction was further verified by conditional logistic regression. Significant allelic association was found for markers RS1912960 (in GABRA4; P = .01) and HCV9866022 (in GABRR2; P = .04). The geno-PDT found significant genotypic association for HCV8262334 (in GABRA2), RS1912960 and RS2280073 (in GABRA4), and RS2617503 and RS12187676 (in GABRB2). Consistent with the allelic and genotypic association results, EMDR confirmed the main effect at RS1912960 (in GABRA4). EMDR also identified a significant two-locus gene-gene effect model involving RS1912960 in GABRA4 and RS2351299 in GABRB1. Further support for this two-locus model came from both the multilocus geno-PDT and the APL test, which indicated a common genotype and haplotype combination positively associated with disease. Finally, these results were also consistent with the results from the conditional logistic regression, which confirmed the interaction between GABRA4 and GABRB1 (odds ratio = 2.9 for interaction term; P = .002). Through the convergence of all analyses, we conclude that GABRA4 is involved in the etiology of autism and potentially increases autism risk through interaction with GABRB1. These results support the hypothesis that GABA receptor subunit genes are involved in autism, most likely via complex gene-gene interactions. PMID:16080114

Ma, D Q; Whitehead, P L; Menold, M M; Martin, E R; Ashley-Koch, A E; Mei, H; Ritchie, M D; Delong, G R; Abramson, R K; Wright, H H; Cuccaro, M L; Hussman, J P; Gilbert, J R; Pericak-Vance, M A

2005-07-15

129

Identical Splicing of Aberrant Epidermal Growth Factor Receptor Transcripts from Amplified Rearranged Genes in Human Glioblastomas  

Microsoft Academic Search

The epidermal growth factor receptor gene has been found to be amplified and rearranged in human glioblastomas in vivo. Here we present the sequence across a splice junction of aberrant epidermal growth factor receptor transcripts derived from corresponding and uniquely rearranged genes that are coamplified and coexpressed with non-rearranged epidermal growth factor receptor genes in six primary human glioblastomas. Each

Noriaki Sugawa; A. Jonas Ekstrand; C. David James; V. Peter Collins

1990-01-01

130

CRDB: database of chemosensory receptor gene families in vertebrate.  

PubMed

Chemosensory receptors (CR) are crucial for animals to sense the environmental changes and survive on earth. The emergence of whole-genome sequences provides us an opportunity to identify the entire CR gene repertoires. To completely gain more insight into the evolution of CR genes in vertebrates, we identified the nearly all CR genes in 25 vertebrates using homology-based approaches. Among these CR gene repertoires, nearly half of them were identified for the first time in those previously uncharacterized species, such as the guinea pig, giant panda and elephant, etc. Consistent with previous findings, we found that the numbers of CR genes vary extensively among different species, suggesting an extreme form of 'birth-and-death' evolution. For the purpose of facilitating CR gene analysis, we constructed a database with the goals to provide a resource for CR genes annotation and a web tool for exploring their evolutionary patterns. Besides a search engine for the gene extraction from a specific chromosome region, an easy-to-use phylogenetic analysis tool was also provided to facilitate online phylogeny study of CR genes. Our work can provide a rigorous platform for further study on the evolution of CR genes in vertebrates. PMID:22393364

Dong, Dong; Jin, Ke; Wu, Xiaoli; Zhong, Yang

2012-02-29

131

Properties of gene expression including the non-functional binding of transcription factors to DNA  

NASA Astrophysics Data System (ADS)

Many eukaryotic transcription factors bind to DNA sequences with a remarkable lack of specificity. This suggests that non-functional binding between transcription factors and DNA might not have the detrimental effect on regulation one would naively assume results from competition for binding. In fact, if binding to DNA protects transcription factors from degradation, the number and binding affinity of these 'decoy' binding sites should have no influence on the copy number of transcription factors available for regulation. We calculate the influence of adding decoy binding sites on several important aspects of gene expression including the noise, the time to reach steady state, and bimodal switch rates. Analyzing these effects could shed some light on how a gene functions in the 'dressed' environment of a genomic background.

Burger, Anat; Walczak, Aleksandra; Wolynes, Peter

2012-02-01

132

A family with a new elastin gene mutation: broad clinical spectrum, including sudden cardiac death.  

PubMed

Supravalvular aortic stenosis is associated with the Williams-Beuren syndrome, but it also occurs in a non-syndromatic congenital form. An elastin gene mutation of chromosome 7q11.23 is responsible in both cases. The vascular features are identical. These patients have a higher risk of sudden death, particularly when undergoing diagnostic or surgical procedures. We report the account of a family with a new mutation in the elastin gene. Screening over three generations revealed eight affected individuals. The cardiac and vascular malformations ranged from mild asymptomatic supravalvular aortic stenosis and isolated dysplastic atrioventricular valves to diffuse arterial hypoplasia. Two infants presented arteries affected at multiple locations, including the left coronary artery. Both died of sudden cardiac death and myocardial ischaemia, one while under general anaesthesia for cardiac catheterisation, and the other perioperatively. We discuss the pathophysiological aspects in these patients that deserve consideration before any general anaesthesia is administered. PMID:21080980

Jakob, André; Unger, Sheila; Arnold, Raoul; Grohmann, Jochen; Kraus, Cornelia; Schlensak, Christian; Stiller, Brigitte

2010-11-16

133

Chromosomal localization of the human V3 pituitary vasopressin receptor gene (AVPR3) to 1q32  

SciTech Connect

Vasopressin exerts its physiological effects on liver metabolism, fluid osmolarity, and corticotrophic response to stress through a set of at least three receptors, V1a, V2, and V3 (also called V1b), respectively. These receptors constitute a distinct group of the superfamily of G-protein-coupled cell surface receptors. When bound to vasopressin, they couple to G proteins activating phospholipase C for the V1a and V3 types and adenylate cyclase for the V2. The vasopressin receptor subfamily also includes the receptor for oxytocin, a structurally related hormone that signals through the activation of phospholipase C. The chromosomal position of the V2 receptor gene has been assigned to Xq28-qter by PCR-based screening of somatic cell hybrids, whereas the oxytocin receptor gene has been mapped to chromosome 3q26.2 by fluorescence in situ hybridization (FISH). The chromosomal location of the V1a gene is currently unknown. We recently cloned the cDNA and the gene coding for the human pituitary-specific V3 receptor (HGMW-approved symbol AVPR3). We report here the chromosomal localization of this gene by two distinct in situ hybridization techniques using radioactive and fluorescent probes. 11 refs., 1 fig.

Rousseau-Merck, M.F.; Derre, J.; Berger, R. [INSERM, Paris (France)] [and others

1995-11-20

134

The nicotinic acetylcholine receptor CHRNA5/A3/B4 gene cluster: dual role in nicotine addiction and lung cancer.  

PubMed

More than 1 billion people around the world smoke, with 10 million cigarettes sold every minute. Cigarettes contain thousands of harmful chemicals including the psychoactive compound, nicotine. Nicotine addiction is initiated by the binding of nicotine to nicotinic acetylcholine receptors, ligand-gated cation channels activated by the endogenous neurotransmitter, acetylcholine. These receptors serve as prototypes for all ligand-gated ion channels and have been extensively studied in an attempt to elucidate their role in nicotine addiction. Many of these studies have focused on heteromeric nicotinic acetylcholine receptors containing ?4 and ?2 subunits and homomeric nicotinic acetylcholine receptors containing the ?7 subunit, two of the most abundant subtypes expressed in the brain. Recently however, a series of linkage analyses, candidate-gene analyses and genome-wide association studies have brought attention to three other members of the nicotinic acetylcholine receptor family: the ?5, ?3 and ?4 subunits. The genes encoding these subunits lie in a genomic cluster that contains variants associated with increased risk for several diseases including nicotine dependence and lung cancer. The underlying mechanisms for these associations have not yet been elucidated but decades of research on the nicotinic receptor gene family as well as emerging data provide insight on how these receptors may function in pathological states. Here, we review this body of work, focusing on the clustered nicotinic acetylcholine receptor genes and evaluating their role in nicotine addiction and lung cancer. PMID:20685379

Improgo, Ma Reina D; Scofield, Michael D; Tapper, Andrew R; Gardner, Paul D

2010-06-04

135

Simulation of E. coli Gene Regulation including Overlapping Cell Cycles, Growth, Division, Time Delays and Noise  

PubMed Central

Due to the complexity of biological systems, simulation of biological networks is necessary but sometimes complicated. The classic stochastic simulation algorithm (SSA) by Gillespie and its modified versions are widely used to simulate the stochastic dynamics of biochemical reaction systems. However, it has remained a challenge to implement accurate and efficient simulation algorithms for general reaction schemes in growing cells. Here, we present a modeling and simulation tool, called ‘GeneCircuits’, which is specifically developed to simulate gene-regulation in exponentially growing bacterial cells (such as E. coli) with overlapping cell cycles. Our tool integrates three specific features of these cells that are not generally included in SSA tools: 1) the time delay between the regulation and synthesis of proteins that is due to transcription and translation processes; 2) cell cycle-dependent periodic changes of gene dosage; and 3) variations in the propensities of chemical reactions that have time-dependent reaction rates as a consequence of volume expansion and cell division. We give three biologically relevant examples to illustrate the use of our simulation tool in quantitative studies of systems biology and synthetic biology.

Luo, Ruoyu; Ye, Lin; Tao, Chenyang; Wang, Kankan

2013-01-01

136

Prevalence of known prognostic factors in female breast carcinoma including oestrogen receptor, progesterone receptor and Her-2/neu status--a study in a tertiary care centre.  

PubMed

Breast cancer is second most common cancer in Indian women. It is often curable by various treatment modalities when detected in early stage. Prognosis and selection of therapy in breast cancer depends upon various factors including clinical parameters, histopathological subtype and molecular characteristics of primary tumour. The aim of this study was to determine the prevalence of different prognostics factors including immunohistochemical marker ie, oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (Her-2/neu) status in female breast carcinoma in a tertiary care centre. In this study 80 females patients who were found to have carcinoma of breast by fine needle aspiration cytology (FNAC) and consequently confirmed by histopathology were followed up for one year. Immunohistochemical staining for molecular markers like oestrogen receptor (ER), progesterone receptor (PR) and Her-2/neu were done in selected 48 cases. Various clinical parameters, cytopathological and hispathological findings as well as immunohistochemical studies were correlated to know the prevalence of these important prognostic factors. It was found that majority of patients were under 50 years of age group with high parity status. Significant patients had breast lump > 4 cm in size. Infiltrating duct carcinoma not otherwise specified (NOS) was the most common histological type showing predominantly microscopic grade II as per Nottingham's Modification of Bloom Richardson grading system. Immunohistochemistry showed 75% ER positivity, 66.66% PR positivity and 25% Her-2/neu positivity. PMID:23936949

Chakrabarti, Suchismita; Karmakar, Rupam; Barui, Gopinath; Maity, Pradip Kumar; Bandyopadhyay, Anindya; Roy, Anup

2012-12-01

137

Molecular diagnostics for congenital hearing loss including 15 deafness genes using a next generation sequencing platform  

PubMed Central

Background Hereditary hearing loss (HL) can originate from mutations in one of many genes involved in the complex process of hearing. Identification of the genetic defects in patients is currently labor intensive and expensive. While screening with Sanger sequencing for GJB2 mutations is common, this is not the case for the other known deafness genes (> 60). Next generation sequencing technology (NGS) has the potential to be much more cost efficient. Published methods mainly use hybridization based target enrichment procedures that are time saving and efficient, but lead to loss in sensitivity. In this study we used a semi-automated PCR amplification and NGS in order to combine high sensitivity, speed and cost efficiency. Results In this proof of concept study, we screened 15 autosomal recessive deafness genes in 5 patients with congenital genetic deafness. 646 specific primer pairs for all exons and most of the UTR of the 15 selected genes were designed using primerXL. Using patient specific identifiers, all amplicons were pooled and analyzed using the Roche 454 NGS technology. Three of these patients are members of families in which a region of interest has previously been characterized by linkage studies. In these, we were able to identify two new mutations in CDH23 and OTOF. For another patient, the etiology of deafness was unclear, and no causal mutation was found. In a fifth patient, included as a positive control, we could confirm a known mutation in TMC1. Conclusions We have developed an assay that holds great promise as a tool for screening patients with familial autosomal recessive nonsyndromal hearing loss (ARNSHL). For the first time, an efficient, reliable and cost effective genetic test, based on PCR enrichment, for newborns with undiagnosed deafness is available.

2012-01-01

138

Identification of novel androgen receptor target genes in prostate cancer  

PubMed Central

Background The androgen receptor (AR) plays critical roles in both androgen-dependent and castrate-resistant prostate cancer (PCa). However, little is known about AR target genes that mediate the receptor's roles in disease progression. Results Using Chromatin Immunoprecipitation (ChIP) Display, we discovered 19 novel loci occupied by the AR in castrate resistant C4-2B PCa cells. Only four of the 19 AR-occupied regions were within 10-kb 5'-flanking regulatory sequences. Three were located up to 4-kb 3' of the nearest gene, eight were intragenic and four were in gene deserts. Whereas the AR occupied the same loci in C4-2B (castrate resistant) and LNCaP (androgen-dependent) PCa cells, differences between the two cell lines were observed in the response of nearby genes to androgens. Among the genes strongly stimulated by DHT in C4-2B cells – D-dopachrome tautomerase (DDT), Protein kinase C delta (PRKCD), Glutathione S- transferase theta 2 (GSTT2), Transient receptor potential cation channel subfamily V member 3 (TRPV3), and Pyrroline-5-carboxylate reductase 1 (PYCR1) – most were less strongly or hardly stimulated in LNCaP cells. Another AR target gene, ornithine aminotransferase (OAT), was AR-stimulated in a ligand-independent manner, since it was repressed by AR siRNA knockdown, but not stimulated by DHT. We also present evidence for in vivo AR-mediated regulation of several genes identified by ChIP Display. For example, PRKCD and PYCR1, which may contribute to PCa cell growth and survival, are expressed in PCa biopsies from primary tumors before and after ablation and in metastatic lesions in a manner consistent with AR-mediated stimulation. Conclusion AR genomic occupancy is similar between LNCaP and C4-2B cells and is not biased towards 5' gene flanking sequences. The AR transcriptionally regulates less than half the genes nearby AR-occupied regions, usually but not always, in a ligand-dependent manner. Most are stimulated and a few are repressed. In general, response is stronger in C4-2B compared to LNCaP cells. Some of the genes near AR-occupied regions appear to be regulated by the AR in vivo as evidenced by their expression levels in prostate cancer tumors of various stages. Several AR target genes discovered in the present study, for example PRKCD and PYCR1, may open avenues in PCa research and aid the development of new approaches for disease management.

Jariwala, Unnati; Prescott, Jennifer; Jia, Li; Barski, Artem; Pregizer, Steve; Cogan, Jon P; Arasheben, Armin; Tilley, Wayne D; Scher, Howard I; Gerald, William L; Buchanan, Grant; Coetzee, Gerhard A; Frenkel, Baruch

2007-01-01

139

Gene number determination and genetic polymorphism of the gamma delta T cell co-receptor WC1 genes  

Technology Transfer Automated Retrieval System (TEKTRAN)

Background WC1 co-receptors belong to the scavenger receptor cysteine-rich superfamily and are encoded by a multi-gene family. Expression of particular WC1 genes defines functional subpopulations of WC1+ '' T cells. Our previous study identified partial sequences for 13 different WC1 genes by annota...

140

Functions of duplicated genes encoding CCAP receptors in the red flour beetle, Tribolium castaneum.  

PubMed

Crustacean cardioactive peptide (CCAP) is a nonapeptide originally isolated from the shore crab, Carcinus maenas, based on its cardioacceleratory activity. This peptide is highly conserved in insects and other arthropods. In insects CCAP also has an essential role in ecdysis behavior. We previously identified two homologous genes, ccapr-1 and ccapr-2, encoding putative CCAP receptors in the red flour beetle, Tribolium castaneum. In contrast, some insects, including Drosophila melanogaster, carry only one gene encoding a CCAP receptor. Phylogenetic analysis of putative CCAP receptor orthologs reveals a number of independent gene duplications in several insect lineages. In this study, we confirmed that CCAP activates both putative T. castaneum receptors in a heterologous expression system. RNA interference (RNAi) of ccapr-1 and ccapr-2 revealed that ccapr-2 is essential for eclosion behavior in T. castaneum, while RNAi for ccapr-1 did not result in any abnormal phenotype. In vivo cardioacceleratory activity of exogenously applied CCAP was abolished by RNAi of ccapr-2, but not by that of ccapr-1. Thus, only ccapr-2 mediates the cardioacceleratory function, ccapr-1 having apparently lost both functions for eclosion behavior and for cardioacceleration since the recent gene duplication event. PMID:21708161

Li, Bin; Beeman, Richard W; Park, Yoonseong

2011-06-15

141

Association of 5HT1B receptor gene and antisocial behavior in alcoholism  

Microsoft Academic Search

Summary. The 5-HT1B receptor gene has been postulated to play a modulatory role in alcohol consumption and alcohol dependence, and was considered a candidate gene for alcoholism. More recently, the association of the 5-HT receptor gene polymorphism and antisocial personality traits in alcoholism has been discussed. This possible association was studied using material from our gene bank for alcoholism. The

M. Soyka; U. W. Preuss; G. Koller; P. Zill; B. Bondy

2004-01-01

142

Gene methylation of oestrogen and epidermal growth factor receptors in neoplastic and perineoplastic breast tissues.  

PubMed Central

Oestrogen receptor (ER) and epidermal growth factor receptor (EGFR) gene methylation was evaluated in neoplastic and perineoplastic breast tissues from 20 patients. In both tissues, ER gene methylation was inversely correlated with protein levels, while EGFR gene methylation was not. A preferential ER gene hypomethylation was found in neoplastic tissues, suggesting a significant role in neoplastic transformation.

Petrangeli, E.; Lubrano, C.; Ravenna, L.; Vacca, A.; Cardillo, M. R.; Salvatori, L.; Sciarra, F.; Frati, L.; Gulino, A.

1995-01-01

143

Odorant receptor gene choice is reset by nuclear transfer from mouse olfactory sensory neurons  

Microsoft Academic Search

Of the ~1,000 odorant receptor (OR) genes in the mouse genome, an olfactory sensory neuron (OSN) is thought to express one gene, from one allele. This is reminiscent of immunoglobulin and T-cell receptor genes, which undergo DNA rearrangements in lymphocytes. Here, we test the hypothesis that OR gene choice is controlled by DNA rearrangements in OSNs. Using permanent genetic marking,

Jinsong Li; Tomohiro Ishii; Paul Feinstein; Peter Mombaerts

2004-01-01

144

Odorant receptor gene choice and axonal wiring in mice with deletion mutations in the odorant receptor gene SR1.  

PubMed

In the mouse, a mature olfactory sensory neuron (OSN) of the main olfactory epithelium (MOE) expresses one allele of one of the 1200 odorant receptor (OR) genes in the genome. The mechanisms that underlie the one receptor-one neuron rule remain poorly understood. A popular experimental paradigm for OR gene choice is to delete an OR coding region by gene targeting or in a transgene. Here we have applied this ?OR paradigm to SR1, also known as MOR256-3 or Olfr124. This gene is expressed in OSNs of the MOE, and in ~50% of the OSNs of the septal organ. In heterozygous ?SR1 mice, we observe an unprecedented biallelic expression rate of 30% at the SR1 locus. In homozygous ?SR1 mice, we find a significant increase in the number of septal organ OSNs that undergo apoptosis. As a population, ?SR1 OSNs project their axons to 81-85 glomeruli in each half of the OB, and coexpress at least 77 OR genes as evaluated by single-cell molecular analysis. There are no obvious or simple rules for the set of OR genes that are coexpressed with the ?SR1 allele. The frequencies of coexpression are different for ?SR1 OSNs in the septal organ compared to those in the MOE. We propose that there are as many as five scenarios for the fate of individual ?SR1 OSNs. PMID:23688909

Fuss, Stefan H; Zhu, Yan; Mombaerts, Peter

2013-05-18

145

A new class of obesity genes encodes leukocyte adhesion receptors.  

PubMed

Obesity is a complex disease, and multiple genes contribute to the trait. The description of five genes (ob, db, tub, Ay, and fat) responsible for distinct syndromes of spontaneous monogenic obesity in mice has advanced our knowledge of the genetics of obesity. However, many other genes involved in the expression of this disease remain to be determined. We report here the identification of an additional class of genes involved in the regulation of adipose tissue mass. These genes encode receptors mediating leukocyte adhesion. Mice deficient in intercellular adhesion molecule-1 became spontaneously obese in old age on normal mouse chow or at a young age when provided with a diet rich in fat. Mice deficient in the counterreceptor for intercellular adhesion molecule-1, the leukocyte integrin alphaMbeta2 (Mac-1), showed a similar obesity phenotype. Since all mice consumed approximately the same amount of food as controls, the leukocyte function appears to be in regulating lipid metabolism and/or energy expenditure. Our results indicate that (i) leukocytes play a role in preventing excess body fat deposition and (ii) defects in leukocyte adhesion receptors can result in obesity. PMID:9207125

Dong, Z M; Gutierrez-Ramos, J C; Coxon, A; Mayadas, T N; Wagner, D D

1997-07-01

146

Sheep exhibit novel variations in the organization of the mammalian type II gonadotropin-releasing hormone receptor gene.  

PubMed

Species-specific differences in genes encoding type II GnRH receptor indicate that a functional hepta-helical receptor is produced in monkeys but not in rodents, cows, chimpanzees, or humans. To further investigate the extent of evolutionary differences, we sequenced the type II GnRH receptor gene from wild-type Soay sheep. The gene was isolated by long-distance PCR using primers to PEX11beta and RBM8A genes known to flank type II GnRH receptor gene homologues. The gene spans 5.7-kb DNA and was sequenced after shot-gun subcloning. Its novel features include absence of a Pit-1 transcription factor binding site, a premature stop codon (TAG) in exon 1, an in-frame deletion of 51 bp (17 codons) in exon 2, and several nonconservative codon changes. Sheep breed variation in the gene was assessed using genomic DNA in PCR-restriction digest assays for the premature stop codon and in a PCR assay for the deletion. Both characteristics were present in all 15 breeds tested. Receptor gene expression was investigated using poly-A(+) RNA Northern analysis, RT-PCR, and in situ hybridization. An oligonucleotide probe to exon 1 revealed an alternative transcript in testis but not in pituitary gland. No transcripts in testis or pituitary were detectable using an exon 2-3 probe. All tissues examined including multiple brain areas and gonadotrope-enriched cell cultures were negative for type II GnRH receptor in RT-PCR. Testis and pituitary sections were negative with exon 1 riboprobes and exon 1 or 2-3 oligonucleotide probes in in situ hybridization. A hepta-helical type II GnRH receptor is therefore not expressed from this sheep gene. PMID:14749360

Gault, Paula M; Morgan, Kevin; Pawson, Adam J; Millar, Robert P; Lincoln, Gerald A

2004-01-28

147

The ?3-adrenergic receptor gene and obesity in a population sample of African Americans  

Microsoft Academic Search

OBJECTIVE: To examine the role of the Trp64Arg polymorphism in the ?3-adrenergic receptor gene and the ?3-adrenergic receptor gene locus in obesity-related traits in African Americans.SUBJECTS: A total of 687 individuals representing 193 African American families who were residents of metropolitan Chicago.MEASUREMENTS: Genotyping of the Trp64Arg polymorphism in the ?3-adrenergic receptor gene and three microsatellite markers flanking the ?3-adrenergic receptor

WL Lowe; CN Rotimi; A Luke; X Guo; X Zhu; AG Comuzzie; TS Schuh; S Halbach; TJ Kotlar; RS Cooper

2001-01-01

148

Discovery of three novel G-protein-coupled receptor genes.  

PubMed

We report here the molecular cloning, tissue distribution, and chromosomal localization of novel genes encoding G-protein-coupled receptors (GPCRs). A search of a mouse database of expressed sequence tags revealed an EST partially encoding a GPCR, which was used to screen a mouse genomic library to obtain the translational open reading frame (ORF). The resultant clone, GPR27, contained an intronless ORF, encoding a receptor of 379 amino acids. In an alternate strategy, human genomic DNA was subjected to polymerase chain reaction (PCR) amplification, using degenerate oligonucleotides based on GPR1. Two PCR products partially encoding GPCRs were isolated and used to screen a genomic library to obtain the translational ORF. One of the resultant clones, GPR30, contained an intronless ORF encoding a receptor of 375 amino acids. The other clone, GPR35, also contained an intronless ORF encoding a receptor of 309 amino acids. Transcripts corresponding to GPR27 and GPR30 were detected in several areas of human and rat CNS, While GPR35 expression was detected only in the rat intestine. Through fluorescence in situ hybridization analysis the gene encoding GPR30 was localized to chromosome 7p22 and GPR35 to chromosome 2q37.3. PMID:9479505

O'Dowd, B F; Nguyen, T; Marchese, A; Cheng, R; Lynch, K R; Heng, H H; Kolakowski, L F; George, S R

1998-01-15

149

Kinin B1 receptor gene ablation affects hypothalamic CART productionb.  

PubMed

A role for the kinin B1 receptor in energy-homeostatic processes was implicated in previous studies; notably, the studies where kinin B1 receptor knockout mice (B1-/-) were shown to have impaired adiposity, impaired leptin and insulin production, lower feed efficiency, protection from liver steatosis and diet-induced obesity when fed a high fat diet (HFD). In particular, in a model where the B1 receptor is expressed exclusively in the adipose tissue, it rescues the plasma insulin concentration and the weight gain seen in wild type mice. Taking into consideration that leptin participates in the formation of hypothalamic nuclei, which modulate energy expenditure, and feeding behavior, we hypothesized that these brain regions could also be altered in B1-/- mice. We observed for the first time a difference in the gene expression pattern of cocaine and amphetamine related transcript (CART) in the (lateral hypothalamic area (LHA) resulting from the deletion of the kinin B1 receptor gene. The correlation between CART expression in the LHA and the thwarting of diet-induced obesity corroborates independent correlations between CART and obesity. Furthermore, it seems to indicate that the mechanism underlying the 'lean' phenotype of B1-/- mice does not stem solely from changes in peripheral tissues but may also receive contributions from changes in the hypothalamic machinery involved in energy homeostasis processes. PMID:23585179

Torres, Hugo A M; Louise Motta, Fabiana; Sales, Vicencia Micheline; Batista, Carolina; da Silva, Joelcimar M; Vignoli, Thiago; Barnabé, Gabriela F; Goeldner, Francine O; D'Almeida, Vânia; Bittencourt, Jackson C; Sinigaglia-Coimbra, Rita; Bader, Michael; Mello, Luiz Eugênio A M; Pesquero, João Bosco

2013-07-01

150

Epigenetic regulation of kappa opioid receptor gene in neuronal differentiation  

Microsoft Academic Search

The gene of mouse kappa opioid receptor (KOR) utilizes two promoters, P1 and P2. P1 is active in various brain areas and constitutively in P19 mouse embryonal carcinoma cells. P2 is active in limited brain stem areas of adult animals and only in late differentiated cells of P19 induced for neuronal differentiation in the presence of nerve growth factor (NGF).

S. W. Park; Y. He; S. G. Ha; H. H. Loh; L.-N. Wei

2008-01-01

151

Interleukin1 receptor antagonist gene polymorphism and gingivitis in children  

Microsoft Academic Search

AIM: To investigate the role of the polymorphism of a variable numbers of tandem repeats of interleukin-1 receptor antagonist gene (IL-1RN) on gingivitis in children. MATERIALS AND METHODS: A total of 146 Caucasian subjects (98 subjects with gingivitis and 48 controls) aged 8-12 years, were enrolled. Plaque and Calculus Indices were recorded to assess the oral hygiene. Gingival and Bleeding

M Dashash; DB Drucker; IV Hutchinson; AS Blinkhorn

2007-01-01

152

Regulation of Expression of the Human Erythropoietin Receptor Gene  

Microsoft Academic Search

Interactions between erythropoietin (Epo) and its receptor (EpoR) are critical for the normal proliferation and differentiation of erythroid progenitor cells. EpoR is expressed in low numbers during early stages of erythroid maturation, while higher levels are expressed during later stages, suggesting that the expression of the EpoR gene is tightly regulated throughout erythropoiesis. We used the TF-1 erythroleukemia cell line

Stuart S. Winter; Thad Howard; Russell E. Ware

1996-01-01

153

Dopamine D 2 -receptor gene polymorphisms in scandinavian chronic alcoholics  

Microsoft Academic Search

Alterations in the dopamine system have been hypothesized as a predisposing factor in alcoholism. The presence of the TaqI A1 and B1 alleles adjacent to the dopamine D2-receptor gene (DRD2) was studied in Scandinavian alcoholic inpatients (n=74), alcoholics autopsied at a forensic clinic (n=19) and controls (n=81). There were no significant differences between controls and the alcoholics, but a tendecy

T. Geijer; J. Neiman; U. Rydberg; A. Gyllander; E. Jösson; G. Sedvall; P. Valverius; L. Terenius

1994-01-01

154

Insight into adenosine receptor function using antisense and gene-knockout approaches.  

PubMed

The extensive role of adenosine in discriminating input from the extracellular environment is effected through a series of cell membrane-spanning proteins--the adenosine A1, A2A, A2B and A3 receptors. New genetic and epigenetic tools have emerged that facilitate the elucidation of the function of these receptors with greater specificity than is generally possible with traditional antagonist drugs. These tools include antisense oligonucleotides (epigenetic) and gene 'knockin' and 'knockout' mice (genetic) and are discussed in this article by Jonathan Nyce. PMID:10101969

Nyce, J W

1999-02-01

155

Evolution of Olfactory Receptor Genes in Primates Dominated by Birth-and-Death Process  

PubMed Central

Olfactory receptor (OR) is a large family of G protein–coupled receptors that can detect odorant in order to generate the sense of smell. They constitute one of the largest multiple gene families in animals including primates. To better understand the variation in odor perception and evolution of OR genes among primates, we computationally identified OR gene repertoires in orangutans, marmosets, and mouse lemurs and investigated the birth-and-death process of OR genes in the primate lineage. The results showed that 1) all the primate species studied have no more than 400 intact OR genes, fewer than rodents and canine; 2) Despite the similar number of OR genes in the genome, the makeup of the OR gene repertoires between different primate species is quite different as they had undergone dramatic birth-and-death evolution with extensive gene losses in the lineages leading to current species; 3) Apes and Old World monkey (OWM) have similar fraction of pseudogenes, whereas New World monkey (NWM) have fewer pseudogenes. To measure the selective pressure that had affected the OR gene repertoires in primates, we compared the ratio of nonsynonymous with synonymous substitution rates by using 70 one-to-one orthologous quintets among five primate species. We found that OR genes showed relaxed selective constraints in apes (humans, chimpanzees, and orangutans) than in OWMs (macaques) and NWMs (marmosets). We concluded that OR gene repertoires in primates have evolved in such a way to adapt to their respective living environments. Differential selective constraints might play important role in the primate OR gene evolution in each primate species.

Dong, Dong; He, Guimei; Zhang, Shuyi

2009-01-01

156

Overexpression of thyroid hormone receptor alpha 1 during zebrafish embryogenesis disrupts hindbrain patterning and implicates retinoic acid receptors in the control of hox gene expression.  

PubMed

Nuclear receptors play key roles in anterior/posterior (A/P) axis formation during vertebrate embryogenesis. Within this gene family, retinoic acid receptors and retinoic acid itself have profound influences on the establishment of the A/P axis. Thyroid hormone receptors are expressed during early periods of development, long before the establishment of the thyroid gland, and are able to interact with retinoic acid receptors. Here we examined the ability of the thyroid hormone receptor alpha 1 to affect early embryonic development by mRNA injection of either repressor or activator forms of the thyroid hormone receptor. Overexpression of either the thyroid hormone receptor alpha 1 or a constitutive repressor form, v-erbA, caused a swelling in the rostral hindbrain. These defects were associated with disorganization and loss of rhombomere borders as well as an increase in the number of acetylcholine esterase positive cells. This phenotype correlated with a reduction in hoxa1 expression during gastrulation. Furthermore, injection of either thyroid hormone receptor alpha 1 or v-erbA mRNA repressed a reporter gene that contained a retinoic acid response element, demonstrating the ability of the thyroid hormone receptor alpha 1 to repress retinoic acid signaling during gastrulation. In contrast, embryos treated with retinoic acid alone or embryos injected with thyroid hormone receptor alpha 1 and treated with the thyroid hormone analog TRIAC displayed a similar set of defects, including loss of the midbrain-hindbrain border and severe disruption of the rostral hindbrain. These studies support the involvement of retinoic acid and its receptors in the direct control of Hox gene expression and the early patterning of the zebrafish central nervous system. PMID:10448709

Essner, J J; Johnson, R G; Hackett, P B

1999-07-01

157

Rabbit calcium-sensing receptor (CASR) gene: chromosome location and evidence for related genes.  

PubMed

Diverse cellular functions are regulated by the calcium-sensing receptor, encoded by the CASR gene, which plays an important role in calcium homeostasis. Here we provide the sequence for exon VII of the rabbit CASR gene and show that it is 91% identical to the human gene at the nucleotide level, and 95% identical at the amino acid level. The gene was mapped by fluorescence in situ hybridization, using a cosmid isolated from a genomic library, to chromosome 14q11 and this was confirmed independently by PCR amplification of flow sorted chromosomes. In addition, the cosmid detected sites with lower frequencies on four other chromosomes: 3q, 5p, 8p, and 13p. Two of these sites (5p and 13p) were also detected by a related but unidentical cosmid, and map to regions that are homologous to the mouse calcium-sensing receptor related sequences (Casr-rs); suggesting that they may represent CASR-related sequences in the rabbit. The data support the presence of a family of genes related to the calcium-sensing receptor in the G-protein coupled receptor (GPCR) superfamily, as well as extend the existing knowledge of homology for several human and rabbit chromosomes. PMID:10575221

Martin-DeLeon, P A; Canaff, L; Korstanje, R; Bhide, V; Selkirk, M; Hendy, G N

1999-01-01

158

Somatic and germline mutations of the TSH receptor gene in thyroid diseases  

SciTech Connect

Under physiological circumstances, thyrotropin (TSH) is the primary hormone that controls thyroid function and growth. TSH acts by binding to its receptor at the basolateral membrane of thyroid follicular cells. The TSH receptor is a member of the large family of G protein-coupled receptors, which share a similar structural pattern: seven transmembrane segments connected by three extra and three intracellular loops. Together with the receptors for other glycoprotein hormones LH/CG and FSH, the TSH receptor has a long aminoterminal domain that has been shown to encode the specificity for hormone recognition and binding. The G protein-coupled receptors share a common mode of intracellular signalling: They control the on/off state of a variety of trimeric G proteins (G{alpha}{beta}{gamma}) by stimulating the exchange of GDP for GTP on the {alpha} subunit (G{alpha}). The result is that G{alpha} or G{beta}{gamma}, after dissociation of the trimer, will interact with downstream effectors of the receptor. In the case of the TSH receptor, the main G protein involved is Gs, which activates adenylyl cyclase via Gs{alpha}. In some species, including man, the TSH receptor is also capable of activating phospholipase C (via Gq), thus stimulating the production of diacylglycerol and inositolphosphate (IP{sub 3}). However, higher concentrations of TSH are required to activate phospholipase C, compared with adenylyl cyclase. As a consequence, the main second messenger of TSH effects on the human thyroid is cyclic AMP. The present review will summarize recent findings identifying mutations of the TSH receptor gene as a cause for thyroid diseases. 59 refs., 4 figs.

Van Sande, J.; Parma, J.; Tonacchera, M. [and others

1995-09-01

159

The histamine H3 receptor: from gene cloning to H3 receptor drugs  

Microsoft Academic Search

Since the cloning of the histamine H3 receptor cDNA in 1999 by Lovenberg and co-workers, this histamine receptor has gained the interest of many pharmaceutical companies as a potential drug target for the treatment of various important disorders, including obesity, attention-deficit hyperactivity disorder, Alzheimer's disease, schizophrenia, as well as for myocardial ischaemia, migraine and inflammatory diseases. Here, we discuss relevant

Remko A. Bakker; Henk Timmerman; Iwan J. P. de Esch; Rob Leurs

2005-01-01

160

Structure, characterization, and expression of the rat oxytocin receptor gene.  

PubMed Central

The multiple hormonal and neurotransmitter functions of the nonapeptide oxytocin are mediated by specific oxytocin receptors (OTRs). In most target tissues, the number of OTRs is strongly regulated. Specifically, in the uterus, a dramatic OTR upregulation precedes the onset of parturition. To study the molecular mechanisms underlying OTR regulation, we have isolated and characterized recombinant bacteriophage lambda EMBL3 genomic clones containing the rat OTR gene, using sequence information derived from a human myometrial OTR cDNA. The rat OTR gene spans > 20 kb and contains three exons. A 97-bp intron is in the 5' untranslated region and a > 12-kb intron interrupts the coding region between transmembrane domains 6 and 7. The promoter region lacks an apparent TATA or CCAAT box but contains multiple putative interleukin-response elements [six NF-IL6 (C/EBP beta) and four APRF (STAT3) binding motifs], supporting the notion that interleukins may mediate labor induction via transcriptional activation of the OTR gene. The predicted amino acid sequence is 93% identical to the human OTR sequence but only 48% and 38% identical to the rat V1 and V2 vasopressin receptor sequences, respectively. At parturition, the OTR gene is highly expressed in the rat uterus and gives rise to at least three transcripts (2.9, 4.8, and 6.7 kb) which differ in the length of their 3' untranslated regions. Images Fig. 3 Fig. 4 Fig. 5

Rozen, F; Russo, C; Banville, D; Zingg, H H

1995-01-01

161

The cps gene cluster of Salmonella strain LT2 includes a second mannose pathway: sequence of two genes and relationship to genes in the rfb gene cluster  

Microsoft Academic Search

We report the presence in Salmonella enterica strain LT2 (serovar thyphimurium) of duplicate genes for two steps in the synthesis of GDP-mannose. The previously known genes, rfbK (phosphomannomutase) and rfbM (mannose-l-phosphate guanyltransferase), are part of the gene cluster for the O antigen. The two new genes, cpsB and cpsG, respectively, are thought to be part of the gene cluster for

Gordon Stevenson; Sang Jun Lee; Lajwant K. Romana; Peter R. Reeves

1991-01-01

162

T-cell receptor gene rearrangement analysis in the primary cutaneous T-cell lymphoma  

Microsoft Academic Search

Object: The present paper is to evaluate the significance of T-cell receptor (TCR) gene rearrangements in primary cutaneous\\u000a T-cell lymphomas (PCTCL) as detected by analysis of Southern Blot (SBA) and polymerase chain reaction (PCR). Patients and\\u000a Methods: Skin specimens and peripheral blood samples were taken from 44 patients with PCTCL, including 30 patients with mycosis\\u000a fungoides (MF), 2 patients with

Bingsen Qiu; Ping Wang; Hongyang Gao; Yifei Shang; Liangzhong Xu

1997-01-01

163

Analysis of Neuropeptide S Receptor Gene (NPSR1) Polymorphism in Rheumatoid Arthritis  

Microsoft Academic Search

BackgroundPolymorphism in the neuropeptide S receptor gene NPSR1 is associated with asthma and inflammatory bowel disease. NPSR1 is expressed in the brain, where it modulates anxiety and responses to stress, but also in other tissues and cell types including lymphocytes, the lungs, and the intestine, where it appears to be up-regulated in inflammation. We sought to determine whether genetic variability

Mauro D'Amato; Marco Zucchelli; Maria Seddighzadeh; Francesca Anedda; Staffan Lindblad; Juha Kere; Lars Alfredsson; Lars Klareskog; Leonid Padyukov; Andreas Reif

2010-01-01

164

Sun Exposure, Vitamin D Receptor Gene Polymorphisms, and Breast Cancer Risk in a Multiethnic Population  

Microsoft Academic Search

Considerable evidence indicates that vitamin D may reduce the risk of several cancers, including breast cancer. This study examined associations of breast cancer with sun exposure, the principal source of vitamin D, and vitamin D receptor gene (VDR) polymorphisms (FokI, TaqI, BglI) in a population-based case-control study of Hispanic, African-American, and non-Hispanic White women aged 35-79 years from the San

Esther M. John; Gary G. Schwartz; Jocelyn Koo; Wei Wang; Sue A. Ingles

2007-01-01

165

Evidence that RNA editing modulates splice site selection in the 5HT2C receptor gene  

Microsoft Academic Search

Adenosine to inosine editing of mRNA from the human 5-HT2C receptor gene (HTR2C) occurs at five exonic positions (A-E) in a stable stem-loop that includes the normal 5¢ splice site of intron 5 and is flanked by two alternative splice sites. Using in vitro editing, we identified a novel editing site (F) located in the intronic part of the stem-loop

Rachel Flomen; Joanne Knight; Pak Sham; Robert Kerwin; Andrew Makoff

2004-01-01

166

Posttranscriptional regulation of gene expression in hippocampal neurons by glutamate receptor activation  

Microsoft Academic Search

Previous work from this laboratory has documented that glutamate receptor activation and extracellular calcium entry into hippocampal neurons caused a long-lasting down-regulation of ligatin mRNA and protein. Here, we investigated whether glutamate reduced ligatin mRNA levels by decreasing the transcriptional activity of the gene and\\/or by regulating post-transcriptional RNA processing steps including mRNA stability. Using nuclear run-on assays, it was

Emma R. Jakoi; David M. Panchision; Claudia M. Gerwin; Robert J. DeLorenzo

1995-01-01

167

A novel germline mutation in the TSH receptor gene causes non-autoimmune autosomal dominant hyperthyroidism  

Microsoft Academic Search

Objective: Clinical and genetic investigations were undertaken in a case of familial hyperthyroidism, with onset of thyrotoxic symptoms varying between childhood\\/adolescence. Methods: Automatic sequence analysis was carried out of the TSH receptor (TSHR) gene. Functional studies were undertaken of mutant TSHR in transient expression experiments in COS-7 cells including the evaluation of cAMP accumulation and of protein expression by flow

Luisella Alberti; Maria Carla Proverbio; Sabine Costagliola; Giovanna Weber; Paolo Beck-Peccoz; Giuseppe Chiumello; Luca Persani

2001-01-01

168

Plant Receptor-Like Kinase Gene Family: Diversity, Function, and Signaling  

NSDL National Science Digital Library

A basic feature of all biological systems is the ability to sense and process information from chemical signals via cell-surface receptors. One prevalent class of receptors in both plants and animals is the receptor protein kinases. These proteins contain a signal-binding region located outside the cell linked to a region inside the cell called the protein kinase domain. The protein kinase domain transmits information to other cellular components by catalyzing the transfer of a phosphate group from adenosine triphosphate (ATP) to an amino acid residue on the target proteins. In animals and humans, the well-studied family of receptor tyrosine kinases (RTKs) mediates a wide range of signaling events at the cell surface. The importance of receptor protein kinases in plant biology was revealed by the discovery of a family of more than 400 genes coding for receptor-like kinases (RLKs) present in the recently sequenced genome of the model plant Arabidopsis. Unlike most animal RTKs, the plant RLKs use serine and threonine residues in proteins as targets for phosphorylation. Detailed studies of a handful of plant RLK genes have implicated them in the control of plant growth and development and in responses to pathogens. Multiple signals can be sensed by different RLKs, including peptides produced by neighboring cells, steroid hormones, and pathogen cell-wall proteins and carbohydrates. Major challenges for the future will include understanding the wide range of specific signaling functions performed by this large family of receptors and discovering how the information from this multitude of signal initiation points is integrated by the plant's cells.

Shin-Han Shiu (University of Wisconsin-Madison;The Department of Botany REV); Anthony B. Bleecker (University of Wisconsin-Madison;The Department of Botany REV)

2001-12-18

169

The nuclear receptor liver receptor homolog-1 is an estrogen receptor target gene  

Microsoft Academic Search

Liver receptor homolog-1 (LRH-1) is a nuclear receptor previously known to have distinct functions during mouse development and essential roles in cholesterol homeostasis. Recently, a new role for LRH-1 has been discovered in tumor progression, giving LRH-1 potential transforming functions. In order to identify critical factors stimulating LRH-1 expression leading to deregulated cellular proliferation, we studied its expression and its

Jean-Sébastien Annicotte; Carine Chavey; Nadège Servant; Jacques Teyssier; Aurélie Bardin; Anne Licznar; Eric Badia; Pascal Pujol; Françoise Vignon; Thierry Maudelonde; Gwendal Lazennec; Vincent Cavailles; Lluis Fajas

2005-01-01

170

Leptin receptor gene variation and obesity: lack of association in a white British male population  

Microsoft Academic Search

Leptin, a hormone secreted by adipocytes, plays a pivotal role in the control of body weight. Rodents with mutations in the leptin receptor gene develop morbid obesity. It is possible, therefore, that leptin receptor gene mutations contribute to human obesity. To test this possibility, we determined the entire coding sequence of the human leptin receptor cDNA from peripheral blood lymphocytes

Takanari Gotoda; Brian S. Manning; Anthony P. Goldstone; Helen Imrie; Alison L. Evans; A. Donny Strosberg; Paul M. McKeigue; James Scott; Timothy J. Aitman

1997-01-01

171

The CAG Repeat within the Androgen Receptor Gene and its Relationship to Prostate Cancer  

Microsoft Academic Search

The length of a polymorphic CAG repeat sequence, occurring in the androgen receptor gene, is inversely correlated with transcriptional activity by the androgen receptor. Because heightened androgenic stimulation may increase risk of prostate cancer development and progression, we examined whether shorter CAG repeats in the androgen receptor gene are related to higher risk of prostate cancer. We conducted a nested

Edward Giovannucci; Meir J. Stampfer; Krishna Krithivas; Myles Brown; Adam Brufsky; James Talcott; Charles H. Hennekens; Philip W. Kantoff

1997-01-01

172

Human AT 1 receptor is a single copy gene: Characterization in a stable cell line  

Microsoft Academic Search

To address conflicting reports concerning the number of angiotensin II (AII) receptor type 1 (AT1) coding loci in vertebrates, Southern blot analysis was used to determine the genomic representation of AT1 receptor genes in animals comprising a divergent evolutionary spectrum. The data demonstrate that the AT1 receptor gene is present as a single genomic copy in a broad spectrum of

Nambi Aiyar; Elayne Baker; Hsiao-Ling Wu; Ponnal Nambi; Richard M. Edwards; John J. Trill; Catherine Ellis; Derk J. Bergsma

1994-01-01

173

Homozygosity at the dopamine D3 receptor gene in schizophrenic patients  

Microsoft Academic Search

Dopamine receptors have long been implicated in the etiology of schizophrenia. It has been reported an association of schizophrenia with homozygosity at the dopamine D3 receptor gene locus. We have investigated the distribution of a D3 receptor gene polymorphism (BalI) in 107 schizophrenic Spanish patients and 100 healthy matched controls. No statistically significant differences between the patients and control group

Nuria Durany; Johannes Thome; Antonio Palomo; Paul Foley; Peter Riederer; Felix F. Cruz-Sánchez

1996-01-01

174

[Smallest bitter taste receptor (T2Rs) gene repertoire in carnivores].  

PubMed

Bitter taste reception is presumably associated with dietary selection, preventing animals from ingesting potentially harmful compounds. Accordingly, carnivores, who encounter these toxic substances less often, should have fewer genes associated with bitter taste reception compared with herbivores and omnivores. To investigate the genetic basis of bitter taste reception, we confirmed bitter taste receptor (T2R) genes previously found in the genome sequences of two herbivores (cow and horse), two omnivores (mouse and rat) and one carnivore (dog). We also identified, for the first time, the T2R repertoire from the genome of other four carnivore species (ferret, giant panda, polar bear and cat) and detected 17-20 bitter receptor genes from the five carnivore genomes, including 12-16 intact genes, 0-1 partial but putatively functional genes, and 3-8 pseudogenes. Both the intact T2R genes and the total T2R gene number among carnivores were the smallest among the tested species, supporting earlier speculations that carnivores have fewer T2R genes, herbivores an intermediate number, and omnivores the largest T2R gene repertoire. To further explain the genetic basis for this disparity, we constructed a phylogenetic tree, which showed most of the T2R genes from the five carnivores were one-to-one orthologs across the tree, suggesting that carnivore T2Rs were conserved among mammals. Similarly, the small carnivore T2R family size was likely due to rare duplication events. Collectively, these results strengthen arguments for the connection between T2R gene family size, diet and habit. PMID:23776004

Hu, Ling-Ling; Shi, Peng

2013-06-01

175

Leptin, leptin gene and leptin receptor gene polymorphism in heart failure with preserved ejection fraction.  

PubMed

Heart failure with a normal ejection fraction (HFNEF) is common in obesity and coronary artery disease (CAD). Both ischemia and reperfusion induce leptin (LEP) and leptin receptor (LEPR) gene expression. We aimed to investigate the possible associations of serum leptin, leptin gene and leptin receptor gene polymorphism with HFNEF in patients with CAD. 100 Egyptian CAD patients with HFNEF and 100 healthy subjects (the control group) were genotyped for LEP and LEPR polymorphism. Leptin levels were measured. Serum leptin levels were significantly increased in patients compared to the control group. There was a significant increase in the leptin gene (AA genotype) and the leptin receptor gene (RR genotype) in HFNEF patients compared to the control group. Leptin levels, leptin gene (AA genotype) and LEPR (RR genotype) were more associated with NYHA III than with NYHA I and II. We thus concluded that HFNEF is associated with increased serum leptin levels, and the LEP AA genotype or LEPR RR genotype carries at least a threefold increased risk of developing HFNEF. PMID:21584748

Abd El-Aziz, Tarek A; Mohamed, Randa H; Mohamed, Rasha H; Pasha, Heba F

2011-05-17

176

Overexpression of Cholecystokinin-B\\/ Gastrin Receptor Gene in the Stomach of Naturally Occurring Cholecystokinin-A Receptor Gene Knockout Rats  

Microsoft Academic Search

We examined the cholecystokinin (CCK)-B\\/gastrin receptor, H+\\/K+-ATPase and somatostatin gene expression, the histology and immunohistochemistry of gastrin and somatostatin of the stomach, plasma gastrin levels, and gastric acid secretion in naturally occurring CCK-A receptor gene knockout (Otsuka Long-Evans Tokushima fatty, OLETF) rats. The CCK-B\\/gastrin receptor, H+\\/K+-ATPase and somatostatin mRNAs were determined by Northern transfer analysis. The gastric acid secretion and

Kyoko Miyasaka; Setsuko Kanai; Minoru Ohta; Atsuo Jimi; Akira Kono; Akihiro Funakoshi

1998-01-01

177

Evidence of selection at insulin receptor substrate-1 gene loci.  

PubMed

Type 2 diabetes mellitus (T2DM) is a complex disease characterized by insulin resistance and defect of insulin secretion. The worldwide prevalence of T2DM is steadily increasing. T2DM is also significantly associated with obesity, coronary artery disease (CAD), and metabolic syndrome. There is a clear difference in the prevalence of T2DM among populations, and T2DM is highly heritable. Human adaptations to environmental changes in food supply, lifestyle, and geography may have pressured the selection of genes associated with the metabolism of glucose, lipids, carbohydrates, and energy. The insulin receptor substrate-1 (IRS1) gene is considered a major T2DM gene, and common genetic variations near the IRS1 gene were found to be associated with T2DM, insulin resistance, adiposity, and CAD. Here, we aimed to find evidence of selection at the IRS1 gene loci using the HapMap population data. We investigated a 3-step test procedure-Wright's F statistics (Fst), the long-range haplotype (LRH) test, and the integrated haplotype score (iHS) test-to detect selection at the IRS1 gene loci using the HapMap population data. We observed that 1 CAD-associated SNP (rs2943634) and 1 adiposity- and insulin resistance-associated SNP (rs2943650) exhibited high Fst values. We also found selection at the IRS1 gene loci by the LRH test and the iHS test. These findings suggest evidence of selection at the IRS1 gene loci and that further studies should examine the adaptive evolution of T2DM genes. PMID:22797928

Yoshiuchi, Issei

2012-07-15

178

The low-density lipoprotein receptor gene family: a cellular Swiss army knife?  

Microsoft Academic Search

The low-density lipoprotein receptor gene family is an evolutionarily conserved group of cell-surface receptors produced by mammals and other organisms. Initially thought to be endocytic receptors that mediate the uptake of lipoproteins, recent findings have shown that these receptors have other roles in a range of cellular processes. Among other activities, members of this family act as signal transducers in

Anders Nykjaer; Thomas E. Willnow

2002-01-01

179

Haplotypes that include the integrin alpha 11 gene are associated with tick burden in cattle  

PubMed Central

Background Infestations on cattle by the ectoparasite Boophilus (Rhipicephalus) microplus (cattle tick) impact negatively on animal production systems. Host resistance to tick infestation has a low to moderate heritability in the range 0.13 - 0.64 in Australia. Previous studies identified a QTL on bovine chromosome 10 (BTA10) linked to tick burden in cattle. Results To confirm these associations, we collected genotypes of 17 SNP from BTA10, including three obtained by sequencing part of the ITGA11 (Integrin alpha 11) gene. Initially, we genotyped 1,055 dairy cattle for the 17 SNP, and then genotyped 557 Brahman and 216 Tropical Composite beef cattle for 11 of the 17 SNP. In total, 7 of the SNP were significantly (P < 0.05) associated with tick burden tested in any of the samples. One SNP, ss161109814, was significantly (P < 0.05) associated with tick burden in both the taurine and the Brahman sample, but the favourable allele was different. Haplotypes for three and for 10 SNP were more significantly (P < 0.001) associated with tick burden than SNP analysed individually. Some of the common haplotypes with the largest sample sizes explained between 1.3% and 1.5% of the residual variance in tick burden. Conclusions These analyses confirm the location of a QTL affecting tick burden on BTA10 and position it close to the ITGA11 gene. The presence of a significant association in such widely divergent animals suggests that further SNP discovery in this region to detect causal mutations would be warranted.

2010-01-01

180

Evolution of genes for incretin hormones and their receptors.  

PubMed

The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are essential components in the regulation of blood glucose levels in mammals. These two incretins are produced by evolutionarily related genes and these hormones show similarity in sequence as both are glucagon-like sequences. Genes for these hormones have been identified in a number of diverse vertebrate species indicating that they originated prior to the earliest divergences of vertebrate species. However, analysis of functional and sequence data suggest that each of these hormones acquired incretin activity independently, and only since the divergence of tetrapods from fish. Not only are the hormones related, but so are their receptors. Like the hormones, the incretin action of the receptors is not a product of a shared common ancestral history, as the receptors for GLP-1 and GIP are not most closely related. Further study of the physiological functions of GLP-1 and GIP in additional vertebrates is required to better understand the origin of incretin action. PMID:21094895

Irwin, David M

2010-01-01

181

Perilipin, a critical regulator of fat storage and breakdown, is a target gene of estrogen receptor-related receptor {alpha}  

SciTech Connect

Perilipin is a protein localized on lipid droplet surfaces in adipocytes and steroidogenic cells, playing a central role in regulated lipolysis. Expression of the perilipin gene is markedly induced during adipogenesis. We found that transcription from the perilipin gene promoter is activated by an orphan nuclear receptor, estrogen receptor-related receptor (ERR){alpha}. A response element to this receptor was identified in the promoter region by a gene reporter assay, the electrophoretic-gel mobility-shift assay and the chromatin immunoprecipitation assay. Peroxisome proliferator-activated receptor {gamma} coactivator (PGC)-1{alpha} enhanced, whereas small heterodimer partner (SHP) repressed, the transactivating function of ERR{alpha} on the promoter. Thus, the perilipin gene expression is regulated by a transcriptional network controlling energy metabolism, substantiating the functional importance of perilipin in the maintenance of body energy balance.

Akter, Mst. Hasina; Yamaguchi, Tomohiro; Hirose, Fumiko [Graduate School of Life Science, Himeji Institute of Technology, University of Hyogo, 3-2-1 Koto, Kamigori, Hyogo 678-1297 (Japan); Osumi, Takashi [Graduate School of Life Science, Himeji Institute of Technology, University of Hyogo, 3-2-1 Koto, Kamigori, Hyogo 678-1297 (Japan)], E-mail: osumi@sci.u-hyogo.ac.jp

2008-04-11

182

Intrahepatic expression of genes related to metabotropic receptors in chronic hepatitis  

PubMed Central

AIM: To screen for genes related to metabotropic receptors that might be involved in the development of chronic hepatitis. METHODS: Assessment of 20 genes associated with metabotropic receptors was performed in liver specimens obtained by punch biopsy from 12 patients with autoimmune and chronic hepatitis type B and C. For this purpose, a microarray with low integrity grade and with oligonucleotide DNA probes complementary to target transcripts was used. Evaluation of gene expression was performed in relation to transcript level, correlation between samples and grouping of clinical parameters used in chronic hepatitis assessment. Clinical markers of chronic hepatitis included alanine and aspartate aminotransferase, ?-glutamyltranspeptidase, alkaline phosphatase and cholinesterase activity, levels of iron ions, total cholesterol, triglycerides, albumin, glucose, hemoglobin, platelets, histological analysis of inflammatory and necrotic status, fibrosis according to METAVIR score, steatosis, as well as anthropometric body mass index, waist/hip index, percentage of adipose tissue and liver size in ultrasound examination. Gender, age, concomitant diseases and drugs were also taken into account. Validation of oligonucleotide microarray gene expression results was done with the use of quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The highest (0.002 < P < 0.046) expression among genes encoding main components of metabotropic receptor pathways, such as the ? subunit of G-coupled protein, phosphoinositol-dependent protein kinase or arrestin was comparable to that of angiotensinogen synthesized in the liver. Carcinogenesis suppressor genes, such as chemokine ligand 4, transcription factor early growth response protein 1 and lysophosphatidic acid receptor, were characterized by the lowest expression (0.002 < P < 0.046), while the factor potentially triggering hepatic cancer, transcription factor JUN-B, had a 20-fold higher expression. The correlation between expression of genes of protein kinases PDPK1, phosphoinositide 3-kinase and protein kinase A (Spearman’s coefficient range: 0.762-0.769) confirmed a functional link between these enzymes. Gender (P = 0.0046) and inflammation severity, measured by alanine aminotransferase activity (P = 0.035), were characterized by diverse metabotropic receptor gene expression patterns. The Pearson’s coefficient ranging from -0.35 to 0.99 from the results of qRT-PCR and microarray indicated that qRT-PCR had certain limitations as a validation tool for oligonucleotide microarray studies. CONCLUSION: A microarray-based analysis of hepatocyte metabotropic G-protein-related gene expression can reveal the molecular basis of chronic hepatitis.

Ciesla, Andrzej; Kusmider, Maciej; Faron-Gorecka, Agata; Dziedzicka-Wasylewska, Marta; Bociaga-Jasik, Monika; Owczarek, Danuta; Ciecko-Michalska, Irena; Cibor, Dorota; Mach, Tomasz

2012-01-01

183

A human serotonin 1D receptor variant (5HT1D beta) encoded by an intronless gene on chromosome 6.  

PubMed Central

An intronless gene encoding a serotonin receptor (5HT1D beta) has been cloned and functionally expressed in mammalian fibroblast cultures. Based on the deduced amino acid sequence, the gene encodes a 390-amino acid protein displaying considerable homology, within putative transmembrane domains (approximately 75% identity) to the canine and human 5HT1D receptors. Membranes prepared from CHO cells stably expressing the receptor bound [3H]serotonin with high affinity (Kd 4 nM) and displayed a pharmacological profile consistent, but not identical, with that of the characterized serotonin 5HT1D receptor. Most notably, metergoline and serotonergic piperazine derivatives, as a group, display 3- to 8-fold lower affinity for the 5HT1D beta receptor than for the 5HT1D receptor, whereas both receptors display similar affinities for tryptamine derivatives, including the antimigraine drug sumatriptan. Northern blot analysis revealed an mRNA of approximately 5.5 kilobases expressed in human and monkey frontal cortex, medulla, striatum, hippocampus and amygdala but not in cerebellum, olfactory tubercle, and pituitary. The 5HT1D beta gene maps to human chromosome 6. The existence of multiple neuronal 5HT1D-like receptors may help account for some of the complexities associated with [3H]serotonin binding patterns in native membranes. Images

Demchyshyn, L; Sunahara, R K; Miller, K; Teitler, M; Hoffman, B J; Kennedy, J L; Seeman, P; Van Tol, H H; Niznik, H B

1992-01-01

184

Sequence-specific DNA binding of the progesterone receptor to the uteroglobin gene: effects of hormone, antihormone and receptor phosphorylation.  

PubMed Central

The effects of ligand binding and receptor phosphorylation on the interaction of progesterone receptor with specific DNA sequences in the uteroglobin gene were studied by nitro-cellulose filter binding and DNase I footprinting. High affinity sites were mapped upstream from the transcription start and in the first intron. They contained a common TGTTCACT sequence. These sites were occupied with similar affinity by the receptor, either in its free state, or complexed with the hormone or an antagonist (RU486); and also by receptor which had been phosphorylated in vivo in a hormone-dependent manner. In all cases identical footprints were observed. These experiments led to the following conclusions. The hormone-dependency of receptor binding to DNA or chromatin is observed in intact cells and in crude cellular extracts but not with purified receptor. Thus in situ, the unliganded receptor probably interacts with some nuclear component(s) which stabilizes it in a 'non-activated' form (non-chromatin and non-DNA binding form). When isolated, the receptor may undergo activation, even in the absence of the hormone. Binding by receptor of an antihormone (and possibly receptor phosphorylation) exerts an effect on gene transcription through a mechanism which is different from (and probably follows) receptor interaction with the gene. Images Fig. 1. Fig. 2. Fig. 4. Fig. 5. Fig. 6.

Bailly, A; Le Page, C; Rauch, M; Milgrom, E

1986-01-01

185

Polymorphism and genetic mapping of the human oxytocin receptor gene on chromosome 3  

SciTech Connect

Centrally administered oxytocin has been reported to facilitate affiliative and social behaviors, in functional harmony with its well-known peripheral effects on uterine contraction and milk ejection. The biological effects of oxytocin could be perturbed by mutations occurring in the sequence of the oxytocin receptor gene, and it would be of interest to establish the position of this gene on the human linkage map. Therefore we identified a polymorphism at the human oxytocin receptor gene. A portion of the 3{prime} untranslated region containing a 30 bp CA repeat was amplified by polymerase chain reaction (PCR), revealing a polymorphism with two alleles occurring with frequencies of 0.77 and 0.23 in a sample of Caucasian CEPH parents (n = 70). The CA repeat polymorphism we detected was used to map the human oxytocin receptor to chromosome 3p25-3p26, in a region which contains several important genes, including loci for Von Hippel-Lindau disease (VHL) and renal cell carcinoma. 53 refs., 2 figs., 1 tab.

Michelini, S.; Urbanek, M.; Goldman, D. [National Institute of Health-National Institute of Alcohol Abuse and Alcoholism, Rockville, MD (United States)] [and others

1995-06-19

186

Dissecting the regulation of yeast genes by the osmotin receptor.  

PubMed

The Izh2p protein from Saccharomyces cerevisiae is a receptor for the plant antifungal protein, osmotin. Since Izh2p is conserved in fungi, understanding its biochemical function could inspire novel strategies for the prevention of fungal growth. However, it has been difficult to determine the exact role of Izh2p because it has pleiotropic effects on cellular biochemistry. Herein, we demonstrate that Izh2p negatively regulates functionally divergent genes through a CCCTC promoter motif. Moreover, we show that Izh2p-dependent promoters containing this motif are regulated by the Nrg1p/Nrg2p and Msn2p/Msn4p transcription factors. The fact that Izh2p can regulate gene expression through this widely dispersed element presents a reasonable explanation of its pleiotropy. The involvement of Nrg1p/Nrgp2 in Izh2p-dependent gene regulation also suggests a role for this receptor in regulating fungal differentiation in response to stimuli produced by plants. PMID:18625204

Kupchak, Brian R; Villa, Nancy Y; Kulemina, Lidia V; Lyons, Thomas J

2008-07-14

187

Post-transcriptional regulation of gene expression in hippocampal neurons by glutamate receptor activation.  

PubMed

Previous work from this laboratory has documented that glutamate receptor activation and extracellular calcium entry into hippocampal neurons caused a long-lasting down-regulation of ligatin mRNA and protein. Here, we investigated whether glutamate reduced ligatin mRNA levels by decreasing the transcriptional activity of the gene and/or by regulating post-transcriptional RNA processing steps including mRNA stability. Using nuclear run-on assays, it was demonstrated that transcriptional activity of the ligatin gene was not significantly decreased after glutamate receptor activation. Further, Northern analysis of RNA from neurons maintained in the presence of the transcription inhibitor, alpha-amanitin, showed that glutamate shortened the half life of the ligatin message from 10 h to 58 min. This post-transcriptional destabilization of ligatin mRNA was mimicked by NMDA, dependent on Ca2+, blocked by MK801, and not affected by AMPA and kainic acid, indicating that message stability was governed by changes in intracellular calcium. Moreover, using in situ hybridization and confocal microscopy, we showed that glutamate and NMDA decreased ligatin message within dendritic and somal regions without increasing nuclear levels. These findings demonstrated that glutamate receptor activation altered neuronal gene expression posttranscriptionally by destabilizing mRNA. Our data suggest that post-transcriptional regulation of gene expression may be part of the normal receptor mediated regulatory program of plasticity and provides the first description of a glutamate receptor-modulated, calcium-dependent mechanism which rapidly destabilizes mRNA in neurons. PMID:8653400

Jakoi, E R; Panchision, D M; Gerwin, C M; DeLorenzo, R J

1995-09-25

188

Tazarotene-Induced Gene 1 (TIG1), a Novel Retinoic Acid Receptor-Responsive Gene in Skin  

Microsoft Academic Search

Retinoids exert their effect through ligand-dependent transcription factors, retinoic acid receptors (RAR&?, ?, and ?) and retinoid X receptor (RXR?, ?, and ?), which belong to the superfamily of steroid\\/ thyroid\\/vitamin D3 nuclear receptors. Using a subtraction hybridization approach, we have identified a cDNA sequence, Tazarotene Induced Gene 1 (TIG1), which is highly upregulated in skin raft cultures by an

Sunil Nagpal; Sheetal Patel; Arisa T. Asano; Alan T. Johnson; Madeleine Duvic; Roshantha A. S. Chandraratna

1996-01-01

189

Impact of reference gene selection for type 2 cannabinoid receptor gene expression studies in human spermatozoa.  

PubMed

Quantitative real-time polymerase chain reaction (qRT-PCR) has been employed to study the gene expression profiles in human spermatozoa, but accurate analysis is dependent upon normalisation of data against an endogenous control. ?-Actin (ACTB) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) are the most commonly used reference genes for normalisation of gene expression in human spermatozoa, but the expression of these genes in many tissues has considerable variation under different physiological, pathological and experimental conditions which limits their effectiveness in normalisation. The expression stability of a panel of 12 reference genes was studied in normal and pathological human spermatozoa using geNorm and NormFinder software. Although there were some discrepancies in the ranking of reference gene stability, each software program ranked B2 M, ACTB, CYC1 and 18S RNA within the top 5 and recommended the combined use of at least two reference genes. Normalisation of qRT-PCR data for the cannabinoid receptor type 2 in spermatozoa using the different housekeeping genes demonstrated how, without validation, conflicting results are obtained. We recommend that the arbitrary use of reference genes should be avoided and the validation of reference gene stability should be undertaken prior to every study. For normalisation of CB2 expression, we would recommend using the geometric mean of B2 M and ACTB. PMID:22928818

Amoako, A A; Gebeh, A K; Marczylo, E L; Willets, J M; Elson, J; Marczylo, T H; Konje, J C

2012-08-29

190

Enhancement of gene transactivation activity of androgen receptor by hepatitis B virus X protein  

SciTech Connect

Hepatitis B virus (HBV) X protein (HBx) is a regulatory protein that is required for efficient replication of HBV in its natural host. In this report, we demonstrate by co-immunoprecipitation experiments that HBx can physically bind to the androgen receptor (AR), which is a nuclear hormone receptor that is expressed in many different tissues including the liver. This observation is further supported by confocal microscopy, which reveals that HBx can alter the subcellular localization of the AR both in the presence and in the absence of dihydrotestosterone (DHT). Further studies indicate that HBx can enhance the gene transactivation activity of AR by enhancing its DNA binding activity in a DHT-dependent manner. However, HBx does not remain associated with AR on the DNA. As AR can regulate the expression of a number of cellular genes, our results raise the possibility that HBV pathogenesis may be mediated in part via the interaction between HBx and AR.

Zheng Yanyan [Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, 2011 Zonal Avenue, HMR-401, Los Angeles, CA 90033 (United States); Chen Wenling [Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, 2011 Zonal Avenue, HMR-401, Los Angeles, CA 90033 (United States); Ma, W.-L. Maverick [George Whipple Lab for Cancer Research, Department of Pathology, Urology, Radiation Oncology and the Cancer Center, University of Rochester Medical Center, Rochester, NY (United States); Chang Chawnshang [George Whipple Lab for Cancer Research, Department of Pathology, Urology, Radiation Oncology and the Cancer Center, University of Rochester Medical Center, Rochester, NY (United States); Ou, J.-H. James [Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, 2011 Zonal Avenue, HMR-401, Los Angeles, CA 90033 (United States)]. E-mail: jamesou@hsc.usc.edu

2007-07-05

191

Rapid induction by wounding and bacterial infection of an S gene family receptor-like kinase gene in Brassica oleracea.  

PubMed Central

A receptor-like kinase, SRK, has been implicated in the autoincompatible response that leads to the rejection of self-pollen in Brassica plants. SRK is encoded by one member of a multigene family, which includes several receptor-like kinase genes with patterns of expression very different from that of SRK but of unknown function. Here, we report the characterization of a novel member of the Brassica S gene family, SFR2. RNA gel blot analysis demonstrated that SFR2 mRNA accumulated rapidly in response both to wounding and to infiltration with either of two bacteria: Xanthomonas campestris, a pathogen, and Escherichia coli, a saprophyte. SFR2 mRNA also accumulated rapidly after treatment with salicylic acid, a molecule that has been implicated in plant defense response signaling pathways. A SFR2 promoter and reporter gene fusion was introduced into tobacco and was shown to be induced by bacteria of another genus, Ralstonia (Pseudomonas) solanacearum. The accumulation of SFR2 mRNA in response to wounding and pathogen invasion is typical of a gene involved in the defense responses of the plant. The rapidity of SFR2 mRNA accumulation is consistent with SFR2 playing a role in the signal transduction pathway that leads to induction of plant defense proteins, such as pathogenesis-related proteins or enzymes of phenylpropanoid metabolism.

Pastuglia, M; Roby, D; Dumas, C; Cock, J M

1997-01-01

192

Evolution of dopamine receptor genes of the D1 class in vertebrates.  

PubMed

The receptors of the dopamine neurotransmitter belong to two unrelated classes named D1 and D2. For the D1 receptor class, only two subtypes are found in mammals, the D1A and D1B, receptors, whereas additional subtypes, named D1C, D1D, and D1X, have been found in other vertebrate species. Here, we analyzed molecular phylogeny, gene synteny, and gene expression pattern of the D1 receptor subtypes in a large range of vertebrate species, which leads us to propose a new view of the evolution of D1 dopamine receptor genes. First, we show that D1C and D1D receptor sequences are encoded by orthologous genes. Second, the previously identified Cypriniform D1X sequence is a teleost-specific paralog of the D1B sequences found in all groups of jawed vertebrates. Third, zebrafish and several sauropsid species possess an additional D1-like gene, which is likely to form another orthology group of vertebrate ancestral genes, which we propose to name D1E. Ancestral jawed vertebrates are thus likely to have possessed four classes of D1 receptor genes-D1A, D1B(X), D1C(D), and D1E-which arose from large-scale gene duplications. The D1C receptor gene would have been secondarily lost in the mammalian lineage, whereas the D1E receptor gene would have been lost independently in several lineages of modern vertebrates. The D1A receptors are well conserved throughout jawed vertebrates, whereas sauropsid D1C receptors have rapidly diverged, to the point that they were misidentified as D1D. The functional significance of the D1C receptor loss is not known. It is possible that the function may have been substituted with D1A or D1B receptors in mammals, following the disappearance of D1C receptors in these species. PMID:23197594

Yamamoto, Kei; Mirabeau, Olivier; Bureau, Charlotte; Blin, Maryline; Michon-Coudouel, Sophie; Demarque, Michaël; Vernier, Philippe

2012-11-28

193

Evolution of Dopamine Receptor Genes of the D1 Class in Vertebrates  

PubMed Central

The receptors of the dopamine neurotransmitter belong to two unrelated classes named D1 and D2. For the D1 receptor class, only two subtypes are found in mammals, the D1A and D1B, receptors, whereas additional subtypes, named D1C, D1D, and D1X, have been found in other vertebrate species. Here, we analyzed molecular phylogeny, gene synteny, and gene expression pattern of the D1 receptor subtypes in a large range of vertebrate species, which leads us to propose a new view of the evolution of D1 dopamine receptor genes. First, we show that D1C and D1D receptor sequences are encoded by orthologous genes. Second, the previously identified Cypriniform D1X sequence is a teleost-specific paralog of the D1B sequences found in all groups of jawed vertebrates. Third, zebrafish and several sauropsid species possess an additional D1-like gene, which is likely to form another orthology group of vertebrate ancestral genes, which we propose to name D1E. Ancestral jawed vertebrates are thus likely to have possessed four classes of D1 receptor genes—D1A, D1B(X), D1C(D), and D1E—which arose from large-scale gene duplications. The D1C receptor gene would have been secondarily lost in the mammalian lineage, whereas the D1E receptor gene would have been lost independently in several lineages of modern vertebrates. The D1A receptors are well conserved throughout jawed vertebrates, whereas sauropsid D1C receptors have rapidly diverged, to the point that they were misidentified as D1D. The functional significance of the D1C receptor loss is not known. It is possible that the function may have been substituted with D1A or D1B receptors in mammals, following the disappearance of D1C receptors in these species.

Yamamoto, Kei; Mirabeau, Olivier; Bureau, Charlotte; Blin, Maryline; Michon-Coudouel, Sophie; Demarque, Michael; Vernier, Philippe

2013-01-01

194

Extensive Phenotypic Analysis of a Family with Growth Hormone (GH) Deficiency Caused by a Mutation in the GH-Releasing Hormone Receptor Gene  

Microsoft Academic Search

GH secretion and release are complex phenomena depending on activation of several genes, including those encoding GH, GHRH, and its receptor (GHRH-R). The GH gene, which is the most extensively analyzed sequence in patients with familial GH deficiency (GHD), represents the main known target of mutations. To test the involve- ment of the GHRH-R gene in this disease phenotype, we

IRENE NETCHINE; PHILIPPE TALON; FLORENCE DASTOT; FRANCOISE VITAUX; MICHEL GOOSSENS; SERGE AMSELEM

195

Identification and characterization of the human retinoid X receptor alpha gene promoter.  

PubMed

Retinoid X receptors (RXRs) comprise a family of nuclear retinoid activated transcription factors that are members of the steroid hormone receptor superfamily. RXRs are obligate heterodimerization partners with several other hormone receptor family members, making them critical mediators of a wide range of signaling pathways. Retinoids have been used successfully for the prevention of a number of epithelial cancers, including skin squamous cell carcinoma (SCC). The reduced expression levels of retinoid receptors including RXRalpha, the predominant RXR expressed in skin, is associated with malignancy in skin SCC. In order to study the regulation of RXRalpha in skin SCC carcinogenesis we have previously mapped the majority of the human RXRalpha gene. In the present study we have identified its first exon and promoter region. Exon 1, which contains the translation start site, is located in a highly G+C rich region of the genome at least 58 kb centromeric from exon 2. The promoter region itself is unusually G+C rich (75% G+C in 1200 bp of upstream sequence), has 17 putative SP1 transcription factor binding sites and no TATA or CAAT boxes. Transient transfection experiments with RXRalpha promoter-luciferase reporter constructs in SRB12-p9 skin SCC cells, as well as with PC3 prostate carcinoma cells, revealed that RXRalpha transcription is relatively weak compared to the positive control thymidine kinase (TK) promoter and is stimulated by treatment with all-trans retinoic acid (ATRA), the biologically active form of vitamin A. These results indicate that the RXRalpha gene is transcribed at stable levels, similar to most housekeeping genes, and its transcription is regulated by ATRA. In addition, the 5' untranslated region of RXRalpha is highly G+C rich, resulting in a potentially stable folding pattern, that would place RXRalpha amongst a group of genes that are subject to regulation at the translational level. PMID:16517099

Li, Guojun; Yin, Weihong; Chamberlain, Robert; Hewett-Emmett, David; Roberts, Jennifer N; Yang, Xiulan; Lippman, Scott M; Clifford, John L

2006-03-06

196

Expressed Sequence Tags from Cephalic Chemosensory Organs of the Northern Walnut Husk Fly, Rhagoletis suavis, Including a Putative Canonical Odorant Receptor  

PubMed Central

Rhagoletis fruit flies are important both as major agricultural pests and as model organisms for the study of adaptation to new host plants and host race formation. Response to fruit odor plays a critical role in such adaptation. To better understand olfaction in Rhagoletis, an expressed sequence tag (EST) study was carried out on the antennae and maxillary palps of Rhagoletis suavis (Loew) (Diptera: Tephritidae), a common pest of walnuts in eastern United States. After cDNA cloning and sequencing, 544 ESTs were annotated. Of these, 66% had an open reading frame and could be matched to a previously sequenced gene. Based on BLAST sequence homology, 9% (49 of 544 sequences) were nuclear genes potentially involved in olfaction. The most significant finding is a putative odorant receptor (OR), RSOr1, that is homologous to Drosophila melanogaster Or49a and Or85f. This is the first tephritid OR discovered that might recognize a specific odorant. Other olfactory genes recovered included odorant binding proteins, chemosensory proteins, and putative odorant degrading enzymes.

Ramsdell, Karlene M. M.; Lyons-Sobaski, Sheila A.; Robertson, Hugh M.; Walden, Kimberly K. O.; Feder, Jeffrey L.; Wanner, Kevin; Berlocher, Stewart H.

2010-01-01

197

Regulation of dev, an Operon That Includes Genes Essential for Myxococcus xanthus Development and CRISPR-Associated Genes and Repeats  

Microsoft Academic Search

Received 5 February 2007\\/Accepted 6 March 2007 Expression of dev genes is important for triggering spore differentiation inside Myxococcus xanthus fruiting bodies. DNA sequence analysis suggested that dev and cas (CRISPR-associated) genes are cotranscribed at the dev locus, which is adjacent to CRISPR (clustered regularly interspaced short palindromic repeats). Analysis of RNA from developing M. xanthus confirmed that dev and

Poorna Viswanathan; Kimberly Murphy; Bryan Julien; Anthony G. Garza; Lee Kroos

2007-01-01

198

Expression and retinoic acid regulation of the zebrafish nr2f orphan nuclear receptor genes  

PubMed Central

Background The vertebrate nuclear receptor subfamily 2, group f (nr2f) genes encode orphan receptors that have the capacity to act as negative regulators of retinoic acid (RA) signaling. Results We describe embryonic and larval expression of four of the six zebrafish nr2f genes, nr2f1a, nr2f1b, nr2f2 and nr2f5. These genes show highly regulated patterns of expression within the CNS, including in the developing hindbrain, as well as in the mesoderm and endoderm. We also investigated the role of RA and Fgf signaling in regulating early nr2f gene expression. RA is not required for nr2f expression in the hindbrain; however, exogenous RA can repress this expression. Conversely, we find that RA positively regulates nr2f1a expression in trunk endoderm and mesoderm. Fgf signaling is not required for nr2f expression onset in the hindbrain; however, it may play a role in maintaining rhombomere-specific expression. Conclusions We report detailed expression analysis of four nr2f genes in all three germ layers. The onset of nr2f expression in the hindbrain does not require RA or Fgf signals. Our finding that RA positively regulates nr2f1a expression in the trunk supports the possibility that Nr2fs function in a negative feedback loop to modulate RA signaling in this region.

Love, Crystal E.; Prince, Victoria E.

2012-01-01

199

Structure and transcription of the mouse erythropoietin receptor gene.  

PubMed

The complete gene encoding the mouse erythropoietin receptor was isolated by using a cDNA probe derived from a mouse erythroleukemia (MEL) cell library. The gene spans approximately 5 kilobases and is present in a single copy per haploid genome. It contains eight exons, and the nucleotide sequence of the coding region from the genomic DNA is identical to the sequence of one of the MEL cDNA clones except for a single amino acid substitution (Leu----Val) at codon 163. There is a cluster of three major transcriptional start sites approximately 150 nucleotides upstream of the initiator ATG codon which is conserved in erythropoietin-dependent and -independent erythroleukemic cells, in MEL cells at different stages of differentiation, and in normal bone marrow cells. The promoter region contains a potential binding site for Sp1, erythroid-specific transcription factor GF-1, and several CACCC boxes, but not typical TATA or CAAT sequences. A fusion gene containing 452 nucleotides of 5' noncoding sequence linked to a promoterless human growth hormone gene directed the transcription of the latter in MEL cells but not in mouse fibroblasts, T cells, B cells, or macrophagelike cells, suggesting that this promoter functions in an erythroid-specific manner. PMID:2162479

Youssoufian, H; Zon, L I; Orkin, S H; D'Andrea, A D; Lodish, H F

1990-07-01

200

Deletion including the oligophrenin-1 gene associated with enlarged cerebral ventricles, cerebellar hypoplasia, seizures and ataxia  

Microsoft Academic Search

Non-specific X-linked mental retardation is a heterogeneous group of disorders with an incidence of approximately 1 in 500 males. A recently identified gene in Xq12, encoding a Rho-GTPase-activating protein, was found to be mutated in individuals with mental retardation. We describe here two sisters with a 46,XY karyotype and a microdeletion of the oligophrenin-1 gene and 1.1 Mb of flanking

D Tentler; P Gustavsson; J Leisti; M Schueler; J Chelly; E Timonen; G Annerén; HF Willard; N Dahl

1999-01-01

201

Addiction and its reward process through polymorphisms of the D2 dopamine receptor gene: a review.  

PubMed

Since 1990, association studies have amassed strong evidence implicating the D(2) dopamine receptor (DRD2) gene in alcoholism. Specifically, the TaqI A minor (A1) allele of the DRD2 gene has been associated with alcoholism. The DRD2 gene has also been found to be involved in other substance use disorders including cocaine, nicotine and opioid dependence, and obesity. Beyond association studies, pharmacologic studies have shown reduced brain D(2) dopamine receptor numbers in A1(+) allele carriers (A1A1 and A1A2 genotypes) compared to A1(-) allele carriers (A2A2 genotype). Through a number of other approaches, different phenotypes have also been identified in subjects with the A1(+) and A1(-) alleles. These include metabolic, neurophysiological, neuropsychological, personality, stress and treatment studies. It is hypothesized that in an effort to compensate for deficiencies in the dopaminergic system, substance abusers may seek to stimulate the mesocorticolimbic circuits of the brain, long thought to be important in behavioral reward and reinforcement. In effect, one form of the DRD2 gene, the A1 allele, renders the dopaminergic system inefficient and rewards substance abuse that increases brain dopamine levels. PMID:10881203

Noble, E P

2000-03-01

202

Polymorphisms in the vitamin D receptor and the androgen receptor gene associated with the risk of urolithiasis  

Microsoft Academic Search

Transcriptional activity of the vitamin D receptor (VDR) gene is regulated by androgen receptor (AR) gene and both are associated\\u000a with renal stone formation. We examined gene polymorphisms of VDR (PCR-RFLP) and AR (GeneScan analysis) in 125 stone formers\\u000a and 150 controls from north India. Genotype Ff of Fok-I and Tt of Taq-I demonstrated significantly higher risk (P<0.001, OR=3.559\\u000a and

Rama Devi Mittal; D. K. Mishra; P. Srivastava; P. Manchanda; H. K. Bid; R. Kapoor

2010-01-01

203

Receptor protein kinase gene encoded at the self-incompatibility locus  

DOEpatents

Described herein is a S receptor kinase gene (SRK), derived from the S locus in Brassica oleracea, having a extracellular domain highly similar to the secreted product of the S-locus glycoprotein gene.

Nasrallah, June B. (Ithaca, NY); Nasrallah, Mikhail E. (Ithaca, NY); Stein, Joshua (Cortland, NY)

1996-01-01

204

Differential regulation of interleukin-8 gene transcription by death receptor 3 (DR3) and type I TNF receptor (TNFRI)  

Microsoft Academic Search

TL1A induces interleukin-8 (IL-8) secretion in human peripheral blood monocyte-derived macrophage in a dose- and time-dependent manner. Overexpression of its cognate receptor DR3 can induce a higher amount of IL-8 protein secretion than that induced by TNFRI even though both receptors activate IL-8 gene transcription in a similar fashion. The underlying mechanism for the regulation of the IL-8 gene transcription

Wenlynn B. Su; Ying-Hsin Chang; Wan-Wan Lin; Shie-Liang Hsieh

2006-01-01

205

Gene expression profiling of the androgen receptor antagonists flutamide and vinclozolin in zebrafish (Danio rerio) gonads.  

PubMed

The studies presented in this manuscript focus on characterization of transcriptomic responses to anti-androgens in zebrafish (Danio rerio). Research on the effects of anti-androgens in fish has been characterized by a heavy reliance on apical endpoints, and molecular mechanisms of action (MOA) of anti-androgens remain poorly elucidated. In the present study, we examined effects of a short term exposure (24-96h) to the androgen receptor antagonists flutamide (FLU) and vinclozolin (VZ) on gene expression in gonads of sexually mature zebrafish, using commercially available zebrafish oligonucleotide microarrays (4×44K platform). We found that VZ and FLU potentially impact reproductive processes via multiple pathways related to steroidogenesis, spermatogenesis, and fertilization. Observed changes in gene expression often were shared by VZ and FLU, as demonstrated by overlap in differentially-expressed genes and enrichment of several common key pathways including: (1) integrin and actin signaling, (2) nuclear receptor 5A1 signaling, (3) fibroblast growth factor receptor signaling, (4) polyamine synthesis, and (5) androgen synthesis. This information should prove useful to elucidating specific mechanisms of reproductive effects of anti-androgens in fish, as well as developing biomarkers for this important class of endocrine-active chemicals. PMID:21126777

Martinovi?-Weigelt, Dalma; Wang, Rong-Lin; Villeneuve, Daniel L; Bencic, David C; Lazorchak, Jim; Ankley, Gerald T

2010-10-20

206

The role of a mineralocorticoid receptor gene functional polymorphism in the symptom dimensions of persistent ADHD.  

PubMed

Attention-deficit/hyperactivity disorder (ADHD) affects approximately 5 % of school-aged children and 2.5 % of adults. Genetic studies in ADHD have pointed to genes in different neurobiological systems, with relatively small individual effects. The mineralocorticoid receptor is the main receptor involved in the initial triggering of stress response. Therefore, its encoding gene (NR3C2) is a candidate for psychiatric disorder studies, including ADHD, and behavioral phenotypes. There is evidence that the Val allele of the MRI180V polymorphism (rs5522) increases the risk of depression, attention and cognitive deficits. We investigated the possible role of the mineralocorticoid receptor gene in the symptom dimensions and susceptibility to persistent ADHD. We compared genotype and allele frequencies in 478 adult patients with ADHD and 597 controls and symptom dimensions in 449 patients and 132 controls. Diagnoses were based on the DSM-IV criteria. ADHD symptom dimensions were investigated with SNAP-IV for ADHD severity and Barkley scales for severity and impairment. Carriers of the Val allele presented higher inattention, hyperactivity/impulsivity and impairment scores, while genotype and allele frequencies did not differ between patients and controls. These results are consistent with a possible link between genetic variations in the HPA axis and inattention and hyperactivity measures. PMID:22584804

Kortmann, Gustavo Lucena; Contini, Verônica; Bertuzzi, Guilherme Pinto; Mota, Nina Roth; Rovaris, Diego Luiz; Paixão-Côrtes, Vanessa Rodrigues; de Lima, Leandro Leal; Grevet, Eugenio Horacio; Salgado, Carlos Alberto Iglesias; Vitola, Eduardo Schneider; Rohde, Luis Augusto; Belmonte-de-Abreu, Paulo; Bau, Claiton Henrique Dotto

2012-05-15

207

Estrogen receptor ? can selectively repress dioxin receptor-mediated gene expression by targeting DNA methylation  

PubMed Central

Selective inhibitory crosstalk has been known to occur within the signaling pathways of the dioxin (AhR) and estrogen (ER?) receptors. More specifically, ER? represses a cytochrome P450-encoding gene (CYP1A1) that converts cellular estradiol into a metabolite that inhibits the cell cycle, while it has no effect on a P450-encoding gene (CYP1B1) that converts estrodiol into a genotoxic product. Here we show that ER? represses CYP1A1 by targeting the Dnmt3B DNA methyltransferase and concomitant DNA methylation of the promoter. We also find that histone H2A.Z can positively contribute to CYP1A1 gene expression, and its presence at that gene is inversely correlated with DNA methylation. Taken together, our results provide a framework for how ER? can repress transcription, and how that impinges on the production of an enzyme that generates genotoxic estradiol metabolites, and potential breast cancer progression. Finally, our results reveal a new mechanism for how H2A.Z can positively influence gene expression, which is by potentially competing with DNA methylation events in breast cancer cells.

Marques, Maud; Laflamme, Liette; Gaudreau, Luc

2013-01-01

208

Genotype-Phenotype Correlation of 2q37 Deletions Including NPPC Gene Associated with Skeletal Malformations  

PubMed Central

Coordinated bone growth is controlled by numerous mechanisms which are only partially understood because of the involvement of many hormones and local regulators. The C-type Natriuretic Peptide (CNP), encoded by NPPC gene located on chromosome 2q37.1, is a molecule that regulates endochondral ossification of the cartilaginous growth plate and influences longitudinal bone growth. Two independent studies have described three patients with a Marfan-like phenotype presenting a de novo balanced translocation involving the same chromosomal region 2q37.1 and overexpression of NPPC. We report on two partially overlapping interstitial 2q37 deletions identified by array CGH. The two patients showed opposite phenotypes characterized by short stature and skeletal overgrowth, respectively. The patient with short stature presented a 2q37 deletion causing the loss of one copy of the NPPC gene and the truncation of the DIS3L2 gene with normal CNP plasma concentration. The deletion identified in the patient with a Marfan-like phenotype interrupted the DIS3L2 gene without involving the NPPC gene. In addition, a strongly elevated CNP plasma concentration was found in this patient. A possible role of NPPC as causative of the two opposite phenotypes is discussed in this study.

2013-01-01

209

Naturally Occurring Mutations in the Melanocortin Receptor 3 Gene Are Not Associated with Type 2 Diabetes Mellitus in French Caucasians  

Microsoft Academic Search

Familial genetic studies of type 2 diabetes (T2DM) of different human populations, including the French Caucasians, suggested ev- idence for linkage of T2DM and human chromosome 20q13, a region where maps the melanocortin 3 receptor gene (MC3R). Likewise, its homologous MC4R in human obesity, MC3R gene is also a good candidate for genetic susceptibility to glucose intolerance and T2DM. We

EL HABIB HANI; SOPHIE DUPONT; EMMANUELLE DURAND; CHRISTIAN DINA; SOPHIE GALLINA; IRA GANTZ; PHILIPPE FROGUEL

2010-01-01

210

Melanocortin-1 Receptor Gene Variants Determine the Risk of Nonmelanoma Skin Cancer Independently of Fair Skin and Red Hair  

Microsoft Academic Search

Melanocortin-1 receptor (MC1R) gene variants are associated with fair skin and red hair and, independently of these, with cutaneous malignant melanoma. The association of MC1R gene variants with nonmelanoma skin cancer is largely unknown. A total of 838 subjects were included in the present study: 453 patients with nonmelanoma skin cancer and 385 subjects with no skin cancer. The coding

Maarten T. Bastiaens; Jeannet A. C. ter Huurne; Christine Kielich; Nelleke A. Gruis; Rudi G. J. Westendorp; Bert Jan Vermeer; Jan Nico Bouwes Bavinck

2001-01-01

211

Specific Organization of the Negative Response Elements for Retinoic Acid and Thyroid Hormone Receptors in Keratin Gene Family  

Microsoft Academic Search

Retinoic acid and thyroid hormone are important regulators of epidermal growth, differentiation, and homeostasis. Retinoic acid is extensively used in the treatment of many epidermal disorders ranging from wrinkles to skin cancers. Retinoic acid and thyroid hormone directly control the transcription of differentiation-specific genes including keratins. Their effect is mediated through nuclear receptors RAR and T3R. We have previously identified

Nadezda Radoja; Danilo V. Diaz; Todd J. Minars; Irwin M. Freedberg; Miroslav Blumenberg; Marjana Tomic-Canic

1997-01-01

212

Phylogenetic analysis and expression of zebrafish transient receptor potential melastatin family genes.  

PubMed

Background: The transient receptor potential melastatin (TRPM) gene family belongs to the superfamily of nonselective TRP ion channels. TRP channels are cellular sensors, detecting a multitude of inputs, including temperature, light, chemical, and mechanical stimuli. Recent studies revealed diverse roles during development, linking TRP channels to differentiation, proliferation, cell motility, cell death, and survival. A detailed description of this gene family in the zebrafish is still missing. Results: Phylogenetic analysis revealed 11 trpm genes in the zebrafish genome. The zebrafish orthologs of mammalian TRPM1 and TRPM4 are duplicated and quadruplicated, respectively, and TRPM8, a cold sensitive channel has been lost in zebrafish. Whole-mount in situ hybridization experiments revealed dynamic expression pattern of trpm genes in the developing embryo and early larva. Transcripts were mainly found in neural cell clusters, but also in tissues involved in ion homeostasis. Conclusions: Our results suggest a role of TRPM channels in sensory information processing, including vision, olfaction, taste, and mechanosensation. An involvement in developmental processes is likely, as some trpm genes were found to be expressed in differentiating cells. Our data now provide a basis for functional analyses of this gene family of ion channels in the vertebrate model organism Danio rerio. Developmental Dynamics 242:1236-1249, 2013. © 2013 Wiley Periodicals, Inc. PMID:23908157

Kastenhuber, Edda; Gesemann, Matthias; Mickoleit, Michaela; Neuhauss, Stephan C F

2013-09-30

213

Homeodomain binding motifs modulate the probability of odorant receptor gene choice in transgenic mice  

PubMed Central

Odorant receptor (OR) genes constitute with 1200 members the largest gene family in the mouse genome. A mature olfactory sensory neuron (OSN) is thought to express just one OR gene, and from one allele. The cell bodies of OSNs that express a given OR gene display a mosaic pattern within a particular region of the main olfactory epithelium. The mechanisms and cis-acting DNA elements that regulate the expression of one OR gene per OSN – OR gene choice – remain poorly understood. Here, we describe a reporter assay to identify minimal promoters for OR genes in transgenic mice, which are produced by the conventional method of pronuclear injection of DNA. The promoter transgenes are devoid of an OR coding sequence, and instead drive expression of the axonal marker tau-?galactosidase. For four mouse OR genes (M71, M72, MOR23, and P3) and one human OR gene (hM72), a mosaic, OSN-specific pattern of reporter expression can be obtained in transgenic mice with contiguous DNA segments of only ?300 bp that are centered around the transcription start site (TSS). The ?150 bp region upstream of the TSS contains three conserved sequence motifs, including homeodomain (HD) binding sites. Such HD binding sites are also present in the H and P elements, DNA sequences that are known to strongly influence OR gene expression. When a 19mer encompassing a HD binding site from the P element is multimerized nine times and added upstream of a MOR23 minigene that contains the MOR23 coding region, we observe a dramatic increase in the number of transgene-expressing founders and lines and in the number of labeled OSNs. By contrast, a nine-times multimerized 19mer with a mutant HD binding site does not have these effects. We hypothesize that HD binding sites in the H and P elements and in OR promoters modulate the probability of OR gene choice.

Vassalli, Anne; Feinstein, Paul; Mombaerts, Peter

2013-01-01

214

The arthritis severity locus Cia5a regulates the expression of inflammatory mediators including Syk pathway genes and proteases in pristane-induced arthritis  

PubMed Central

Background Cia5a is a locus on rat chromosome 10 that regulates disease severity and joint damage in two models of rheumatoid arthritis, collagen- and pristane-induced arthritis (PIA). In this study, we aimed to identify cellular and molecular processes regulated by Cia5a using microarray-based gene expression analysis of synovial tissues from MHC identical DA (severe erosive disease) and DA.F344(Cia5a) congenics (mild non-erosive disease) rats. Results Synovial tissues from six DA and eight DA.F344(Cia5a) rats were analyzed 21 days after the induction of PIA using the Illumina RatRef-12 BeadChip (21,922 genes) and selected data confirmed with qPCR. There was a significantly increased expression of pro-inflammatory mediators such as Il1b (5-fold), Il18 (3.9-fold), Cxcl1 (10-fold), Cxcl13 (7.5-fold) and Ccl7 (7.9-fold), and proteases like Mmp3 (23-fold), Mmp9 (32-fold), Mmp14 (4.4-fold) and cathepsins in synovial tissues from DA, with reciprocally reduced levels in congenics. mRNA levels of 47 members of the Spleen Tyrosine Kinase (Syk) pathway were significantly increased in DA synovial tissues compared with DA.F344(Cia5a), and included Syk (5.4-fold), Syk-activating receptors and interacting proteins, and genes regulated by Syk such as NFkB, and NAPDH oxidase complex genes. Nuclear receptors (NR) such as Rxrg, Pparg and Rev-erba were increased in the protected congenics, and so was the anti-inflammatory NR-target gene Scd1 (54-fold increase). Tnn (72-fold decrease) was the gene most significantly increased in DA. Conclusions Analyses of gene expression in synovial tissues revealed that the arthritis severity locus Cia5a regulates the expression of key mediators of inflammation and joint damage, as well as the expression of members of the Syk pathway. This expression pattern correlates with disease severity and joint damage and along with the gene accounting for Cia5a could become a useful biomarker to identify patients at increased risk for severe and erosive disease. The identification of the gene accounting for Cia5a has the potential to generate a new and important target for therapy and prognosis.

2012-01-01

215

Corticosteroid receptor gene expression is related to sex and social behaviour in a social fish.  

PubMed

Circulating corticosteroids have been related to social status in a variety of species. However, our understanding of corticosteroid receptor expression and its relationship with sociality is still in its infancy. Knowledge of variation in receptor expression is critical to understand the physiological relevance of differences in circulating corticosteroid concentrations. In this study, we examined corticosteroid receptor gene expression in relation to dominance rank, sex, and social behaviour in the highly social cichlid fish, Neolamprologus pulcher. We examined the relative gene expression of the three known teleost corticosteroid receptors: glucocorticoid receptor 1 (GR1), glucocorticoid receptor 2 (GR2), and the mineralocorticoid receptor (MR) in liver and brain tissue of dominant and subordinate N. pulcher males and females. Phylogenetic analysis revealed the N. pulcher gene originally described as GR2, clustered with other teleost GR1 genes, while the originally-described N. pulcher GR1 gene clustered with the GR2 genes of other teleosts. Therefore we propose a change in the original nomenclature of the N. pulcher GRs: GR1 (formerly GR2) and GR2 (formerly GR1) and adopt this new nomenclature throughout this manuscript. Liver MR transcript levels were higher in males than females, and positively related to submissive behaviour. Liver GR2 (formerly GR1) transcript levels were also higher in males than females. Collectively, the results demonstrate sex differences in corticosteroid receptor abundance, and suggest tissue- and receptor-specific roles for corticosteroid receptors in mediating aspects of social behaviour. PMID:23246501

O'Connor, Constance M; Rodela, Tammy M; Mileva, Viktoria R; Balshine, Sigal; Gilmour, Kathleen M

2012-12-13

216

Nineteen Baculovirus Open Reading Frames, Including LEF-12, Support Late Gene Expression  

PubMed Central

A set of 18 plasmid subclones of the Autographa californica nuclear polyhedrosis virus genome, each containing an identified late expression factor gene (lef), supports expression from a late viral promoter in transient expression assays in the SF-21 cell line derived from Spodoptera frugiperda. We have constructed a further set of plasmids in which each lef open reading frame (ORF) is controlled by the Drosophila melanogaster heat shock protein 70 (hsp70) promoter and epitope tagged. Failure of this set of plasmids to support transient late gene expression, and the inability of the p47 ORF to replace the p47-containing plasmid supplied in the lef plasmid library, led to the identification of a 19th late expression factor gene (lef-12) located adjacent to the p47 gene. The sequence of lef-12 is predicted to encode a protein of 21 kDa with no homology to any previously identified protein. The set of 19 hsp70-controlled lef ORFs (HSEpiHis lef library) supports transient expression from a late viral promoter. lef-12 did not affect expression from an early baculovirus promoter. In TN-368 cells, which are also permissive for virus replication, lef-12 provided a stimulatory effect but did not appear to be essential.

Rapp, Jeffrey C.; Wilson, Joyce A.; Miller, Lois K.

1998-01-01

217

The Dopamine D2 Receptor Gene, Perceived Parental Support, and Adolescent Loneliness: Longitudinal Evidence for Gene-Environment Interactions  

ERIC Educational Resources Information Center

|Background: Loneliness is a common problem in adolescence. Earlier research focused on genes within the serotonin and oxytocin systems, but no studies have examined the role of dopamine-related genes in loneliness. In the present study, we focused on the dopamine D2 receptor gene (DRD2). Methods: Associations among the DRD2, sex, parental…

van Roekel, Eeske; Goossens, Luc; Scholte, Ron H. J.; Engels, Rutger C. M. E.; Verhagen, Maaike

2011-01-01

218

Estrogen receptor a gene polymorphisms (Pvu II and Xba I) influence association between leptin receptor gene polymorphism (Gln223Arg) and bone mineral density in young men  

Microsoft Academic Search

Objective: The peak bone mass is recognized as an important determinant in the development of osteo- porosis. We investigated associations between bone mineral density (BMD) and polymorphisms of the leptin receptor (LEPR) and estrogen receptor a (ERa) genes in young men. Design: BMD, anthropometric characteristics, and serum leptin concentrations were measured in young men and compared with regard to the

CLINICAL S TUDY; Jung-Min Koh; Duk J Kim; Jeong S Hong; Joong Y Park; Shin-Yoon Kim; Ghi S Kim

219

Mechanisms of the mouse orphan nuclear receptor TR2-11-mediated gene suppression.  

PubMed

The mouse orphan nuclear receptor TR2-11 functions as a repressor for reporter genes containing a direct repeat-5 or direct repeat-4 hormone response element. The functional domains responsible for its suppressive activity are defined, including the DNA-binding domain and the ligand-binding domain. The C-terminal 30 amino acid residues can be deleted without compromising its suppressive activity, whereas a deletion for 40 amino acids completely abolishes the suppressive activity and receptor dimerization, and reduces the DNA-binding affinity. Point mutation at three conserved leucine residues located on the predicted dimer interface abolishes the suppressive activity, receptor dimerization and its DNA binding property. However, mutation at two consecutive glutamate residues located within the hinge between the last two helices of the ligand-binding domain (helix 10 and helix 11 according to the human retinoid receptor X alpha structure) drastically reduces its DNA-binding affinity and abrogates the suppressive activity without compromising its ability to dimerize, indicating that receptor dimerization property can be functionally uncoupled from its suppressive activity. A transferable, active silencing activity is encoded within the DEF segment of the receptor molecule, as evidenced by the suppression of a GAL4 reporter by a chimeric protein containing the DNA-binding domain of GAL4 and the DEF segment of TR2-11. Moreover, the C-terminal 49 amino acid sequence is required for this trans-suppressive activity. It is suggested that TR2-11 functions as a repressor, mediated by mechanisms requiring high affinity DNA binding, receptor dimerization, and active silencing. PMID:9660764

Chinpaisal, C; Lee, C H; Wei, L N

1998-07-17

220

Genes Expressed in Pinus radiata Male Cones Include Homologs to Anther-Specific and Pathogenesis Response Genes1  

PubMed Central

We describe the isolation and characterization of 13 cDNA clones that are differentially expressed in male cones of Pinus radiata (D. Don). The transcripts of the 13 genes are expressed at different times between meiosis and microspore mitosis, timing that corresponds to a burst in tapetal activity in the developing anthers. In situ hybridization showed that four of the genes are expressed in the tapetum, while a fifth is expressed in tetrads during a brief developmental window. Six of the seven cDNAs identified in database searches have striking similarity to genes expressed in angiosperm anthers. Seven cDNAs are homologs of defense and pathogen response genes. The cDNAs identified are predicted to encode a chalcone-synthase-like protein, a thaumatin-like protein, a serine hydrolase thought to be a putative regulator of programmed cell death, two lipid-transfer proteins, and two homologs of the anther-specific A9 genes from Brassica napus and Arabidopsis. Overall, our results support the hypothesis that many of the reproductive processes in the angiosperms and gymnosperms were inherited from a common ancestor.

Walden, Adrian R.; Walter, Christian; Gardner, Richard C.

1999-01-01

221

Adult attachment and gene polymorphisms of the dopamine D4 receptor and serotonin transporter (5-HTT)  

Microsoft Academic Search

Recently, the Dopamine D4 Receptor Gene (DRD4) and the Serotonin Transporter Gene (5-HTT) have been found to be candidate genes for infant attachment disorganization. The present study aimed to explore the relationship of these genes to adult attachment representations. The Adult Attachment Interview was used to assess attachment representations in 167 German adults. DNA from buccal cells was genotyped for

Iris Reiner; Gottfried Spangler

2010-01-01

222

Genomic imprinting of the human serotonin-receptor (HTR2) gene involved in development of retinoblastoma  

Microsoft Academic Search

Epidemiological and genetic studies of retinoblastoma (RB) suggested that imprinted genes might be genetically linked to the RB gene. In this study, we found that the human serotonin-receptor, HTR2, gene, which had been mapped nearby the RB gene on chromosome 13, was expressed only in human fibroblasts with a maternal allele and not in cells without a maternal allele. The

Mitsuo V. Kato; Mariko Nagayoshi; Takashi Shimuzu

1996-01-01

223

Leukotriene B4 receptor locus gene characterisation and association studies in asthma  

PubMed Central

Background Polymorphisms spanning genes involved in the production of leukotriene B4 (LTB4) e.g. ALOX5AP and LTA4H are associated with asthma susceptibility, suggesting a role for LTB4 in disease. The contribution of LTB4receptor polymorphism is currently unknown. The aim of this study was to characterise the genes for the two pivotal LTB4 receptors, LTB4R1 and LTB4R2 in lung tissue and determine if polymorphisms spanning these genes are associated with asthma and disease severity. Methods Rapid amplification of cDNA ends (RACE) was used to characterise the LTB4R1 and LTB4R2 gene structure in lung. The LTB4R1/2 locus on chromosome 14q11.2 was screened for polymorphic variation. Six LTB4R single nucleotide polymorphisms (SNPs) were genotyped in 370 Caucasian asthma families and 299 Adult Asthma Individuals (n=1877 total) and were evaluated for association with asthma and severity (BTS) outcome measures using Family Based Association Test, linear regression and chi square. Results LTB4R1 has complex mRNA arrangement including multiple 5?-untranslated exons, suggesting additional levels of regulation. Three potential promoter regions across the LTB4R1/2 locus were identified with some airway cell specificity. 22 SNPs (MAF>0.01) were validated across the LTB4R locus in the Caucasian population. LTB4R1 and LTB4R2 SNPs were not associated with asthma susceptibility, FEV1 or severity. Conclusions LTB4R1 and LTB4R2 shows splice variation in the 5?-untranslated region and multiple promoter regions. The functional significance of this is yet to be determined. Both receptor genes were shown to be polymorphic. LTB4R polymorphisms do not appear to be susceptibility markers for the development of asthma in Caucasian subjects.

2012-01-01

224

A Chemosensory Gene Family Encoding Candidate Gustatory and Olfactory Receptors in Drosophila  

Microsoft Academic Search

A novel family of candidate gustatory receptors (GRs) was recently identified in searches of the Drosophila genome. We have performed in situ hybridization and transgene experiments that reveal expression of these genes in both gustatory and olfactory neurons in adult flies and larvae. This gene family is likely to encode both odorant and taste receptors. We have visualized the projections

Kristin Scott; Roscoe Brady; Anibal Cravchik; Pavel Morozov; Andrey Rzhetsky; Charles Zuker; Richard Axel

2001-01-01

225

Polymorphism of the Androgen Receptor Gene is Associated with Male Pattern Baldness  

Microsoft Academic Search

The common heritable loss of scalp hair known as male pattern baldness or androgenetic alopecia affects up to 80% of males by age 80. A balding scalp is characterized by high levels of the potent androgen dihydrotestosterone and increased expression of the androgen receptor gene. To determine if the androgen receptor gene is associated with male pattern baldness, we compared

Justine A. Ellis; Margaret Stebbing; Stephen B. Harrap

2001-01-01

226

Detection of large deletions in the LDL receptor gene with quantitative PCR methods  

Microsoft Academic Search

BACKGROUND: Familial Hypercholesterolemia (FH) is a common genetic disease and at the molecular level most often due to mutations in the LDL receptor gene. In genetically heterogeneous populations, major structural rearrangements account for about 5% of patients with LDL receptor gene mutations. METHODS: In this study we tested the ability of two different quantitative PCR methods, i.e. Real-Time PCR and

Dorte Damgaard; Peter H Nissen; Lillian G Jensen; Gitte G Nielsen; Anette Stenderup; Mogens L Larsen; Ole Faergeman

2005-01-01

227

Distribution of epidermal growth factor receptor gene amplification in brain tumours and correlation to prognosis  

Microsoft Academic Search

In 75 gliomas and 31 meningiomas, mutations at the epidermal growth factor receptor (EGFR) gene locus were restricted to gliomas. The ligands of this receptor, epidermal growth factor and transforming growth factor alpha, lacked quantitative changes at their loci in gliomas and meningiomas. EGFR gene amplification occurred in astrocytomas, oligodendrogliomas, ependymomas and glioblastomas. The frequency of this mutation significantly increased

Uwe Diedrich; Jens Lucius; Eleonore Baron; Julianne Behnke; Brigitte Pabst; Barbara Zoll

1995-01-01

228

Meltzer PS: Estrogen receptor status in breast cancer is associated with remarkably distinct gene expression patterns  

Microsoft Academic Search

Abstract To investigate the phenotype associated with estrogen receptor,(ER) expression in breast carcinoma, gene expression profiles of 58 node- negative breast carcinomas discordant for ER status were determined using DNA microarray technology. Using artificial neural networks as well as standard hierarchical clustering techniques, the tumors could be classified according to ER status, and a list of genes which discriminate tumors

S Gruvberger; M Ringner; Y Chen; S Panavally; Lh Saal; A Borg; M Ferno; C Peterson

2001-01-01

229

The S-ribonuclease gene of Petunia hybrida is expressed in nonstylar tissue, including immature anthers.  

PubMed Central

To determine the ability of isolated S-locus promoter sequences to direct organ-specific gene expression, we used microprojectile bombardment to introduce chimeric S-allele/beta-glucuronidase genes into different tissues of Petunia hybrida for transient expression. Histochemical staining showed that S-locus/beta-glucuronidase fusions were expressed in pistil, ovary, and petal tissue. No expression of the chimeric genes was detected in leaves or in mature pollen, either by histochemical staining or by fluorescence assays. RNA blot hybridization confirmed that low levels of S-locus mRNA accumulate in petals and ovaries in vivo. Analysis of the expression pattern of S-locus promoter deletions showed that sequences in the immediate vicinity of the TATA box were sufficient to confer qualitatively correct organ-specific expression of beta-glucuronidase. To further investigate the potential for S-ribonuclease expression in pollen, we used the polymerase chain reaction to amplify RNA accumulated in developing anthers. These assays demonstrated that mRNA for the S-ribonuclease accumulates to low levels in developing anthers several days prior to corolla opening and pollen anthesis. We discuss these results in light of current models of self-incompatibility.

Clark, K R; Sims, T L

1994-01-01

230

Rice phosphate transporters include an evolutionarily divergent gene specifically activated in arbuscular mycorrhizal symbiosis  

PubMed Central

Using a genome-wide approach, we asked how many transporter genes contribute to symbiotic phosphate uptake and analyzed their evolutionary conservation. Considering the sequenced rice genome at hand, only the Oryza sativa phosphate transporter (OsPT) gene OsPT11 was specifically induced during the arbuscular mycorrhizal symbiosis. This induction was confined to the root system and was tightly correlated with the degree of root colonization by Glomus intraradices. OsPT11 activation was independent of the nutritional status of the plant and phosphate availability in the rhizosphere. Moreover, infection of roots with the fungal pathogens Rhizoctonia solani and Fusarium moniliforme did not activate OsPT11, corroborating the high signal specificity for OsPT11 activation in the arbuscular mycorrhizal symbiosis. OsPT11 expression complemented a defect in phosphate uptake in a yeast strain mutated in its high-affinity Pi transporter (pho84), thereby confirming its function. Recently, a phosphate transporter gene in potato was shown to be induced during arbuscular mycorrhizal symbiosis. Assessment of the phylogenetic relationship of the rice and potato protein revealed that the rice is nonorthologous to the potato protein. Further, there are no structural commonalities in the promoter regions. Thus, although cytological and physiological features of the arbuscular mycorrhizal symbiosis seem to be conserved, the molecular components may differ significantly between distantly related plant species.

Paszkowski, Uta; Kroken, Scott; Roux, Christophe; Briggs, Steven P.

2002-01-01

231

Recent advances in gene manipulation and nicotinic acetylcholine receptor biology  

PubMed Central

Pharmacological and immunological methods have been valuable for both identifying some native nicotinic acetylcholine receptor (nAChR) subtypes that exist in vivo and determining the neurobiological and behavioral role of certain nAChR subtypes. However, these approaches suffer from shortage of subtype specific ligands and reliable immunological reagents. Consequently, genetic approaches have been developed to complement earlier approaches to identify native nAChR subtypes and to assess the contribution of nAChRs to brain function and behavior. In this review we describe how assembly partners, knock-in mice and targeted lentiviral re-expression of genes have been utilized to improve our understanding of nAChR neurobiology. In addition, we summarize emerging genetic tools in nAChR research.

Tammimaki, Anne; Horton, William J.; Stitzel, Jerry A.

2011-01-01

232

Molecular Cloning of Two Cannabinoid Type 1-like Receptor Genes from the Puffer Fish Fugu rubripes  

Microsoft Academic Search

The puffer fish,Fugu rubripes(Fugu), has been proposed as a model vertebrate genome. We have characterized two putative G-protein-coupled receptor encoding genes, FCB1A and FCB1B, obtained by degenerate PCR and low-stringency hybridization of a Fugu genomic library. These two genes show high homology to the human cannabinoid receptor type 1 (HCB1), but very low homology to the type 2 receptor. The

Fuminori Yamaguchi; Alexander D. Macrae; Sydney Brenner

1996-01-01

233

Expression of cannabinoid receptors and their gene transcripts in human blood cells  

Microsoft Academic Search

1.1. This study shows that the human cannabinoid receptors and their gene transcripts can be analyzed in blood samples when combined with polymerase chain reaction. The results also demonstrate that the expression of the cannabinoid receptors is dependent on gender and ethnic background.2.2. Normal human volunteers who do not use marijuana have genes that encode for the marijuana (cannabinoid) receptor

Emmanuel S. Onaivi; Gautam Chaudhuri; Asli S. Abaci; Monica Parker; Donald H. Manier; Peter R. Martin; John R. Hubbard

1999-01-01

234

Immunophenotypic and antigen receptor gene rearrangement analysis in T cell neoplasia.  

PubMed Central

The author reviews the immunophenotypic profiles displayed by the major clinicopathologic categories of T cell neoplasia, the immunophenotypic criteria useful in the immunodiagnosis of T cell neoplasia, and the contributions made by antigen receptor gene rearrangement analysis to the understanding of T cell neoplasia. Neoplasms belonging to distinct clinicopathologic categories of T cell neoplasia often exhibit characteristic immunophenotypic profiles. Approximately 80% of lymphoblastic lymphomas and 20% of acute lymphoblastic leukemias express phenotypes consistent with prethymic and intrathymic stages of T cell differentiation, including intranuclear terminal deoxynucleotidyl transferase. Cutaneous T cell lymphomas of mycosis fungoides type usually express pan-T cell antigens CD2, CD5, and CD3, often lack the pan-T cell antigen CD7, and usually express the mature, peripheral helper subset phenotype, CD4+ CD8-. Cutaneous T cell lymphomas of nonmycosis fungoides type and peripheral T cell lymphomas often lack one or more pan-T cell antigens and, in addition, occasionally express the anomalous CD4+ CD8+ or CD4- CD8- phenotypes. T gamma-lymphoproliferative disease is divisable into two broad categories: those cases that are CD3 antigen positive and exhibit clonal T cell receptor beta chain (TCR-beta) gene rearrangements and those cases that are CD3 antigen negative and exhibit the TCR-beta gene germline configuration. Human T cell lymphotropic virus-I (HTLV-I) associated Japanese, Carribean, and sporadic adult T cell leukemia/lymphomas usually express pan-T cell antigens, the CD4+ CD8- phenotype, and various T cell-associated activation antigens, including the interleukin-2 receptor (CD25). Immunophenotypic criteria useful in the immunodiagnosis of T cell neoplasia include, in increasing order of utility, T cell predominance, T cell subset antigen restriction, anomalous T cell subset antigen expression, and deletion of one or more pan-T cell antigens. Only in exceptional circumstances do normal, non-neoplastic T cell populations express the CD4- CD8- or the CD4+ CD8+ phenotype and/or lack one or more pan-T cell antigens. T cell receptor beta chain gene rearrangement analysis represents an accurate, objective, and sensitive molecular genetic marker of T cell lineage and clonality that allows discrimination among non-T cell, polyclonal T cell and monoclonal T cell populations. Non-T cells exhibit the TCR-beta gene germline configuration.(ABSTRACT TRUNCATED AT 400 WORDS) Images Figure 3 Figure 6 Figure 7

Knowles, D. M.

1989-01-01

235

Epigenetic Dysregulation of 15q11-13 GABA A Receptor Genes in Autism  

Microsoft Academic Search

\\u000a GABA is the major inhibitory neurotransmitter in the mammalian brain and defects in inhibition have been implicated in autism\\u000a spectrum disorders. GABA inhibition is mediated through a variety of receptor subunit genes. Three GABAA receptor subunit\\u000a genes, GABRB3, GABRA5, and GABRG3 are located on chromosome 15q11-13. In addition to GABAA receptor subunit genes, chromosome\\u000a 15q11-13 contains genes that are expressed

Amber Hogart; Janine M. LaSalle

236

Liver X Receptor Modulation of Gene Expression Leading to Proluteolytic Effects in Primate Luteal Cells1  

PubMed Central

ABSTRACT The expressions of genes involved in cholesterol efflux increase, whereas those involved in extracellular cholesterol uptake decrease, during spontaneous functional regression of the primate corpus luteum (CL). This may result from liver x receptor (LXR) alpha (official symbol NR1H3) and/or beta (official symbol NR1H2) control of luteal gene transcription, because these nuclear receptor superfamily members are key regulators of cellular cholesterol homeostasis. Therefore, studies were conducted to assess endogenous LXR ligands in the primate CL through the luteal phase, and to determine the effect of synthetic or natural LXR ligands on cholesterol efflux and uptake in functional primate luteal cells. Using high-performance liquid chromatography tandem mass spectrometry, three LXR ligands were identified and quantified in the rhesus macaque CL, including 22R-hydroxycholesterol (22ROH), 27-hydroxycholesterol (27OH), and desmosterol. Levels of 22ROH paralleled serum progesterone concentrations, whereas mean levels of 27OH tended to be higher following the loss of progesterone synthesis. Desmosterol was present throughout the luteal phase. Functional macaque luteal cells treated with the synthetic LXR agonist T0901317 or physiologically relevant concentrations of the endogenous luteal ligands 22ROH, 27OH, and desmosterol had increased expression of various known LXR target genes and greater cholesterol efflux. Additionally, T0901317 reduced low-density lipoprotein receptor protein and extracellular low-density lipoprotein uptake, whereas 27OH decreased low-density lipoprotein receptor protein, most likely via a posttranslational mechanism. Collectively, these data support the hypothesis that LXR activation causes increased cholesterol efflux and decreased extracellular cholesterol uptake. In theory, these effects could deplete the primate CL of cholesterol needed for steroidogenesis, ultimately contributing to functional regression.

Bogan, Randy L.; DeBarber, Andrea E.; Hennebold, Jon D.

2011-01-01

237

A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction  

Microsoft Academic Search

The adipocyte-specific hormone leptin, the product of the obese (ob) gene,regulates adipose-tissue mass through hypothalamic effects on satiety and energy expenditure. Leptin acts through the leptin receptor, a single-transmembrane-domain receptor of the cytokine-receptor family. In rodents, homozygous mutations ingenes encoding leptin or the leptin receptor cause early-onsetmorbid obesity, hyperphagia and reduced energy expenditure. These rodents also show hypercortisolaemia, alterations in

Karine Clément; Christian Vaisse; Najiba Lahlou; Sylvie Cabrol; Veronique Pelloux; Dominique Cassuto; Micheline Gourmelen; Christian Dina; Jean Chambaz; Jean-Marc Lacorte; Arnaud Basdevant; Pierre Bougnères; Yves Lebouc; Philippe Froguel; Bernard Guy-Grand

1998-01-01

238

Polymorphism within the bovine estrogen receptor-alpha gene 5'-region.  

PubMed

Due to the functions that estrogens play in the regulation of reproduction, development of the mammary gland, growth and differentiation of cells, estrogen receptors and their genes are considered candidates for the markers of production and functional traits in farm animals, including cattle. In the present study, on the basis of the sequences of the human, ovine, and porcine ER genes, available in the GenBank database, sets of PCR primers were designed and used to amplify the bovine ERalpha gene 5'-region. Seven overlapping fragments of the 5' region of the bovine ERalpha gene were amplified and then sequenced. Altogether, these fragments were composed in the 2853-bp sequence which was deposited in the GenBank database under accession no. AY340597. The sequenced fragment included the noncoding exons A, B, C, their putative promoters, and a part of the coding exon 1. A polymorphism within the 5' region of the bovine ERalpha gene-A/G transition, which could be recognized with RFLP-BglI, lying upstream to the exon C, was identified for the first time using this sequence. PMID:15131353

Szreder, Tomasz; Zwierzchowski, Lech

2004-01-01

239

Gene rearrangements in hormone receptor negative breast cancers revealed by mate pair sequencing  

PubMed Central

Background Chromosomal rearrangements in the form of deletions, insertions, inversions and translocations are frequently observed in breast cancer genomes, and a subset of these rearrangements may play a crucial role in tumorigenesis. To identify novel somatic chromosomal rearrangements, we determined the genome structures of 15 hormone-receptor negative breast tumors by long-insert mate pair massively parallel sequencing. Results We identified and validated 40 somatic structural alterations, including the recurring fusion between genes DDX10 and SKA3 and translocations involving the EPHA5 gene. Other rearrangements were found to affect genes in pathways involved in epigenetic regulation, mitosis and signal transduction, underscoring their potential role in breast tumorigenesis. RNA interference-mediated suppression of five candidate genes (DDX10, SKA3, EPHA5, CLTC and TNIK) led to inhibition of breast cancer cell growth. Moreover, downregulation of DDX10 in breast cancer cells lead to an increased frequency of apoptotic nuclear morphology. Conclusions Using whole genome mate pair sequencing and RNA interference assays, we have discovered a number of novel gene rearrangements in breast cancer genomes and identified DDX10, SKA3, EPHA5, CLTC and TNIK as potential cancer genes with impact on the growth and proliferation of breast cancer cells.

2013-01-01

240

Expression of the human ABCC6 gene is induced by retinoids through the retinoid X receptor  

SciTech Connect

Mutations in the human ABCC6 gene are responsible for the disease pseudoxanthoma elasticum, although Physiological function or substrate of the gene product (an ABC transporter known also as MRP6) is not known. We found that the expression of this gene in cells of hepatic origin (where this gene is predominantly expressed in the body) is significantly upregulated by retinoids, acting as agonists of the retinoid X receptor (RXR) rather than the retinoid A receptor (RAR). The direct involvement of this nuclear receptor in the transcriptional regulation of ABCC6 gene expression was confirmed by transient transfection and chromatin immunoprecipitation assays. This constitutes the first direct proof of previously suggested involvement of nuclear hormone receptors in ABCC6 gene expression and the first identification of a transcription factor which may be relevant to regulation of ABCC6 level in tissues and in some PXE patients.

Ratajewski, Marcin [Laboratory of Transcriptional Regulation, Centre for Medical Biology PAS, Lodz (Poland); Department of Molecular Biophysics, University of Lodz, Lodz (Poland); Bartosz, Grzegorz [Department of Molecular Biophysics, University of Lodz, Lodz (Poland); Pulaski, Lukasz [Laboratory of Transcriptional Regulation, Centre for Medical Biology PAS, Lodz (Poland) and Department of Molecular Biophysics, University of Lodz, Lodz (Poland)]. E-mail: lpulaski@cbm.pan.pl

2006-12-01

241

Two novel aspects of the kinetics of gene expression including miRNAs  

NASA Astrophysics Data System (ADS)

In eukaryotic cells, many genes are transcribed into non-coding RNAs. Small RNAs or, more specifically, microRNAs (miRNAs) form an abundant sub-class of such RNAs. miRNAs are transcribed as long noncoding RNA and then generated via a processing pathway down to the 20-24-nucleotide length. The key ability of miRNAs is to associate with target mRNAs and to suppress their translation and/or facilitate degradation. Using the mean-field kinetic equations and Monte Carlo simulations, we analyze two aspects of this interplay. First, we describe the situation when the formation of mRNA or miRNA is periodically modulated by a transcription factor which itself is not perturbed by these species. Depending on the ratio between the mRNA and miRNA formation rates, the corresponding induced periodic kinetics are shown to be either nearly harmonic or shaped as anti-phase pulses. The second part of the work is related to recent experimental studies indicating that differentiation of stem cells often involves changes in gene transcription into miRNAs and/or the interference between miRNAs, mRNAs and proteins. In particular, the regulatory protein obtained via mRNA translation may suppress the miRNA formation, and the latter may suppress in turn the miRNA-mRNA association and degradation. The corresponding bistable kinetics are described in detail.

Zhdanov, Vladimir P.

2013-04-01

242

Activation of transforming potential of the human insulin receptor gene  

SciTech Connect

A retrovirus containing part of the human insulin receptor (hIR) gene was constructed by replacing ros sequences in the avian sarcoma virus UR2 with hIR cDNA sequences coding for 46 amino acids of the extracellular domain and the entire transmembrane and cytoplasmic domains of the ..beta.. subunit of hIR. The resulting virus, named UIR, contains the hIR sequence fused to the 5' portion of the UR2 gag gene coding for p19. UIR is capable of transforming chicken embryo fibroblasts and promoting formation of colonies in soft agar; however, it does not form tumors in vivo. A variant that arose from the parental UIR is capable of efficiently inducing sarcomas in vivo. UIR-transformed cells exhibit higher rates of glucose uptake and growth than normal cells. The 4-kilobase UIR genome codes for a membrane-associated, glycosylated gag-hIR fusion protein of 75 kDa designated P75/sup gag-hir/. P75/sup gag-hir/ contains a protein tyrosine kinase activity that is capable of undergoing autophosphorylation and of phosphorylating foreign substrates in vitro; it is phosphorylated at both serine and tyrosine residues in vivo

Wang, L.H.; Lin, B.; Jong, S.M.J.; Dixon, D.; Ellis, L.; Roth, R.A.; Rutter, W.J.

1987-08-01

243

A comparison of reptilian and avian olfactory receptor gene repertoires: Species-specific expansion of group ? genes in birds  

Microsoft Academic Search

BACKGROUND: The detection of odorants is mediated by olfactory receptors (ORs). ORs are G-protein coupled receptors that form a remarkably large protein superfamily in vertebrate genomes. We used data that became available through recent sequencing efforts of reptilian and avian genomes to identify the complete OR gene repertoires in a lizard, the green anole (Anolis carolinensis), and in two birds,

Silke S Steiger; Vladimir Y Kuryshev; Marcus C Stensmyr; Bart Kempenaers; Jakob C Mueller

2009-01-01

244

Induction of human liver X receptor alpha gene expression via an autoregulatory loop mechanism.  

PubMed

The liver X receptors (LXRs), members of the nuclear receptor superfamily, play an important role in controlling lipid homeostasis by activating several genes involved in reverse cholesterol transport. These include members of the ATP binding cassette (ABC) superfamily of transporter proteins ABCA1 and ABCG1, surface constituents of plasma lipoproteins like apolipoprotein E, and cholesterol ester transport protein. They also play an important role in fatty acid metabolism by activating the sterol regulatory element-binding protein 1c gene. Here, we identify human LXRalpha (hLXRalpha) as an autoinducible gene. Induction in response to LXR ligands is observed in multiple human cell types including macrophages and occurs within 2--4 h. Analysis of the hLXRalpha promoter revealed three LXR response elements (LXREs); one exhibits strong affinity for both LXRalpha:RXR and LXRbeta:RXR (a type I LXRE), and deletion and mutational studies indicate it plays a critical role in LXR-mediated induction. The other two LXREs are identical to each other, exist within highly conserved Alu repeats, and exhibit selective binding to LXRalpha:RXR (type II LXREs). In transfections, the type I LXRE acts as a strong mediator of both LXRalpha and LXRbeta activity, whereas the type II LXRE acts as a weaker and selective mediator of LXRalpha activity. Our data suggest a model in which LXR ligands trigger an autoregulatory loop leading to selective induction of hLXRalpha gene expression. This would lead to increased hLXRalpha levels and transcription of its downstream target genes such as ABCA1, providing a simple yet exquisite mechanism for cells to respond to LXR ligands and cholesterol loading. PMID:11875109

Li, Yu; Bolten, Charles; Bhat, B Ganesh; Woodring-Dietz, Jessica; Li, Suzhen; Prayaga, Sudhirdas K; Xia, Chunsheng; Lala, Deepak S

2002-03-01

245

Decoy receptor 3 regulates the expression of various genes in rheumatoid arthritis synovial fibroblasts.  

PubMed

Decoy receptor 3 (DcR3), a member of the tumor necrosis factor (TNF) receptor (TNFR) superfamily, lacks the transmembrane domain of conventional TNFRs in order to be a secreted protein. DcR3 competitively binds and inhibits members of the TNF family, including Fas ligand (FasL), LIGHT and TNF-like ligand 1A (TL1A). We previously reported that TNF?-induced DcR3 overexpression in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) protects cells from Fas-induced apoptosis. Previous studies have suggested that DcR3 acting as a ligand directly induces the differentiation of macrophages into osteoclasts. Furthermore, we reported that DcR3 induces very late antigen-4 (VLA--4) expression in THP-1 macrophages, inhibiting cycloheximide-induced apoptosis and that DcR3 binds to membrane-bound TL1A expressed on RA-FLS, resulting in the negative regulation of cell proliferation induced by inflammatory cytokines. In the current study, we used cDNA microarray to search for genes in RA-FLS whose expression was regulated by the ligation of DcR3. The experiments revealed the expression profiles of genes in RA-FLS regulated by DcR3. The profiles showed that among the 100 genes most significantly regulated by DcR3, 45 were upregulated and 55 were downregulated. The upregulated genes were associated with protein complex assembly, cell motility, regulation of transcription, cellular protein catabolic processes, cell membrane, nucleotide binding and glycosylation. The downregulated genes were associated with transcription regulator activity, RNA biosynthetic processes, cytoskeleton, zinc finger region, protein complex assembly, phosphate metabolic processes, mitochondrion, ion transport, nucleotide binding and cell fractionation. Further study of the genes detected in the current study may provide insight into the pathogenesis and treatment of rheumatoid arthritis by DcR3-TL1A signaling. PMID:23912906

Fukuda, Koji; Miura, Yasushi; Maeda, Toshihisa; Takahashi, Masayasu; Hayashi, Shinya; Kurosaka, Masahiro

2013-08-01

246

Association of dopamine receptor gene polymorphisms with the clinical course of Wilson disease.  

PubMed

Background: Dopamine receptor D2 (DRD2) polymorphisms are proposed to be important factors in the presentation of neuropsychiatric symptoms in many disorders, including decreased striatum levels of dopamine D2 receptors in Wilson disease. The present study investigated the association between DRD2 gene polymorphisms and clinical manifestation of Wilson disease. Methods: Analyzing data from 97 symptomatic Wilson disease patients, we investigated the DRD2 gene polymorphisms rs1800497, rs1799732, and rs12364283. We assessed the polymorphisms impact on the phenotypic presentation of the disease. Results: Generally, the DRD2 gene polymorphisms had no impact on the hepatic or neuropsychiatric clinical presentation of Wilson disease. However, rs1799732 deletion allele carriers with neuropsychiatric symptoms had earlier onset of WD symptoms by almost 6 years compared with individuals without this allele (22.5 vs. 28.3 years; P < 0.05). This unfavorable effect of the rs1799732 polymorphism was even more pronounced among adenosine triphosphatase 7B gene (ATP7B) p.H1069Q homozygous patients, in whom carriership of the deletion allele was related to earlier initial neuropsychiatric manifestation by 14 years (18.4 vs. 32.2 years; P < 0.01). Conclusions: Genetic variation of DRD2, specifically the rs1799732 polymorphism, may produce an earlier clinical presentation of Wilson disease neuropsychiatric symptoms and signs that occur in the course of dopaminergic system impairment due to copper accumulation in the brain. We speculate that this effect may be due to the impact of DRD2 polymorphism on dopamine D2 receptor density, but further studies are needed to understand the mechanisms of such phenotypic effects. PMID:23430523

Litwin, T; Gromadzka, G; Samochowiec, J; Grzywacz, A; Cz?onkowski, A; Cz?onkowska, A

2012-07-06

247

Estrogen-related receptor {alpha} modulates the expression of adipogenesis-related genes during adipocyte differentiation  

SciTech Connect

Estrogen-related receptor {alpha} (ERR{alpha}) is an orphan nuclear receptor that regulates cellular energy metabolism by modulating gene expression involved in fatty acid oxidation and mitochondrial biogenesis in brown adipose tissue. However, the physiological role of ERR{alpha} in adipogenesis and white adipose tissue development has not been well studied. Here, we show that ERR{alpha} and ERR{alpha}-related transcriptional coactivators, peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) coactivator-1{alpha} (PGC-1{alpha}) and PGC-1{beta}, can be up-regulated in 3T3-L1 preadipocytes at mRNA levels under the adipogenic differentiation condition including the inducer of cAMP, glucocorticoid, and insulin. Gene knockdown by ERR{alpha}-specific siRNA results in mRNA down-regulation of fatty acid binding protein 4, PPAR{gamma}, and PGC-1{alpha} in 3T3-L1 cells in the adipogenesis medium. ERR{alpha} and PGC-1{beta} mRNA expression can be also up-regulated in another preadipocyte lineage DFAT-D1 cells and a pluripotent mesenchymal cell line C3H10T1/2 under the differentiation condition. Furthermore, stable expression of ERR{alpha} in 3T3-L1 cells up-regulates adipogenic marker genes and promotes triglyceride accumulation during 3T3-L1 differentiation. These results suggest that ERR{alpha} may play a critical role in adipocyte differentiation by modulating the expression of various adipogenesis-related genes.

Ijichi, Nobuhiro [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Ikeda, Kazuhiro [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Horie-Inoue, Kuniko [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Yagi, Ken [Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Okazaki, Yasushi [Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Inoue, Satoshi [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan) and Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan)]. E-mail: INOUE-GER@h.u-tokyo.ac.jp

2007-07-06

248

Discovery of estrogen receptor ? target genes and response elements in breast tumor cells  

Microsoft Academic Search

Background: Estrogens and their receptors are important in human development, physiology and disease. In this study, we utilized an integrated genome-wide molecular and computational approach to characterize the interaction between the activated estrogen receptor (ER) and the regulatory elements of candidate target genes. Results: Of around 19,000 genes surveyed in this study, we observed 137 ER-regulated genes in T-47D cells,

Chin-Yo Lin; Anders Ström; Vinsensius Berlian Vega; Say Li Kong; Ai Li Yeo; Jane S Thomsen; Wan Ching Chan; Balraj Doray; Dhinoth K Bangarusamy; Adaikalavan Ramasamy; Liza A Vergara; Suisheng Tang; Allen Chong; Vladimir B Bajic; Lance D Miller; Edison T Liu

2004-01-01

249

Evaluation of the calcium-sensing receptor gene in idiopathic hypercalciuria and calcium nephrolithiasis  

Microsoft Academic Search

Evaluation of the calcium-sensing receptor gene in idiopathic hypercalciuria and calcium nephrolithiasis.BackgroundCalcium urolithiasis is in part genetically determined and associated with idiopathic hypercalciuria.MethodsWe have used a candidate gene approach to determine whether the calcium-sensing receptor (CaR) gene is linked to idiopathic hypercalciuria and calcium urolithiasis in a cohort of French Canadian sibships with multiple affected members (64 sibships from 55

Martin Petrucci; Patrick Scott; Denis Ouimet; Marie-Lucie Trouvé; Yanick Proulx; Luc Valiquette; Gérald Guay; Alain Bonnardeaux

2000-01-01

250

Developmental regulation of murine mammary progesterone receptor gene expression.  

PubMed

Previously we have shown that in normal murine mammary glands progesterone receptor (PgR) levels are modulated as a function of development and differentiation such that lactating mammary glands do not contain detectable levels of PgR as measured by steroid binding. The objective of the present study was to determine whether the lack of steroid binding in lactating mammary glands was due to the absence of receptor protein and if so whether it was accompanied by an alternation in the pattern of PgR gene expression. Accordingly, we have performed an immunological analysis of murine mammary PgR isolated from different developmental states and have also examined these tissues for PgR gene expression. In mammary tissues from all developmental states other than lactation, immunoreactive PgR corresponding to both A and B forms of the protein were detected. Analysis for PgR mRNA revealed multiple species in mammary tissues and the relative order of abundance of the various transcripts and their sizes were approximately 6.9 greater than 8.7 greater than 3.5 greater than 2.7 greater than 4.2. The 6.9 and 8.7 kilobase transcripts accounted for between 70-80% of total mRNA. All five species of mRNA were detected in tissues from nulliparous mice which decreased dramatically during pregnancy, became undetectable during lactation, and were once again detectable in tissues from mice undergoing lactational involution. Experiments designed specifically to examine the effect of estradiol on mammary PgR mRNA revealed that in contrast to tissues from other developmental states, lactating mammary glands were unable to respond to estradiol with an increase in PgR mRNA. Based on these findings and the fact that estrogenic insensitivity of lactating mammary glands coexists with the presence of ER we propose that in this tissue there is an alteration in the estrogen dependent transcriptional regulation of PgR gene expression. PMID:2190799

Shyamala, G; Schneider, W; Schott, D

1990-06-01

251

Polymorphisms of the dopamine D2 receptor, serotonin transporter, and GABA A receptor ? 3 subunit genes and alcoholism in Mexican-Americans  

Microsoft Academic Search

The etiology of alcohol dependence is a complex interaction of psychosocial and biologic factors. To study the impact of genetic factors that play an important role in an individual's vulnerability to alcohol abuse and dependence, we examined the genetic variations of the major neurotransmitter genes, including the dopamine D2 receptor (DRD2) TaqI A, B, and -141C insertion\\/deletion (Ins\\/Del) polymorphisms, the

Tamiko Konishi; Maria Calvillo; Ai-She Leng; Keh-Ming Lin; Yu-Jui Yvonne Wan

2004-01-01

252

Craniofacial dysmorphogenesis including cleft palate in mice with an insertional mutation in the discs large gene.  

PubMed

The discs large (Dlg) protein, or synapse-associated protein 97 (SAP97), is a member of the membrane-associated guanylate kinase family of multidomain scaffolding proteins which recruits transmembrane and signaling molecules to localized plasma membrane sites. Murine dlg is the homologue of the Drosophila dlg tumor suppressor gene. The loss of dlg function in Drosophila disrupts cellular growth control, apicobasal polarity, and cell adhesion of imaginal disc epithelial cells, resulting in embryonic lethality. In this study, we isolated a mutational insertion in the murine dlg locus by gene trapping in totipotent embryonic stem cells. This insertion results in a truncated protein product that contains the N-terminal three PSD-95/DLG/ZO-1 domains of Dlg fused to the LacZ reporter and subsequently lacks the src homology 3 (SH3), protein 4.1 binding, and guanylate kinase (GUK)-like domains. The Dlg-LacZ fusion protein is expressed in epithelial, mesenchymal, neuronal, endothelial, and hematopoietic cells during embryogenesis. Mice homozygous for the dlg mutation exhibit growth retardation in utero, have hypoplasia of the premaxilla and mandible, have a cleft secondary palate, and die perinatally. Consistent with this phenotype, Dlg-LacZ is expressed in mesenchymal and epithelial cells throughout palatal development. Our genetic and phenotypic analysis of dlg mutant mice suggests that protein-protein interactions involving the SH3, protein 4.1 binding, and/or GUK-like domains are essential to the normal function of murine Dlg within craniofacial and palatal morphogenesis. PMID:11238884

Caruana, G; Bernstein, A

2001-03-01

253

The pharmacophore of a peptoid VEGF receptor 2 antagonist includes both side chain and main chain residues.  

PubMed

Here we identify the pharmacophore in a peptoid that antagonizes Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) in vitro and in vivo. Only three of the side chains in the peptoid are required for activity. Surprisingly, however, main chain atoms also form critical interactions with the receptor. PMID:18653335

Udugamasooriya, D Gomika; Dunham, Geoff; Ritchie, Caroline; Brekken, Rolf A; Kodadek, Thomas

2008-07-10

254

Cooperative demethylation by JMJD2C and LSD1 promotes androgen receptor-dependent gene expression.  

PubMed

Posttranslational modifications of histones, such as methylation, regulate chromatin structure and gene expression. Recently, lysine-specific demethylase 1 (LSD1), the first histone demethylase, was identified. LSD1 interacts with the androgen receptor and promotes androgen-dependent transcription of target genes by ligand-induced demethylation of mono- and dimethylated histone H3 at Lys 9 (H3K9) only. Here, we identify the Jumonji C (JMJC) domain-containing protein JMJD2C as the first histone tridemethylase regulating androgen receptor function. JMJD2C interacts with androgen receptor in vitro and in vivo. Assembly of ligand-bound androgen receptor and JMJD2C on androgen receptor-target genes results in demethylation of trimethyl H3K9 and in stimulation of androgen receptor-dependent transcription. Conversely, knockdown of JMJD2C inhibits androgen-induced removal of trimethyl H3K9, transcriptional activation and tumour cell proliferation. Importantly, JMJD2C colocalizes with androgen receptor and LSD1 in normal prostate and in prostate carcinomas. JMJD2C and LSD1 interact and both demethylases cooperatively stimulate androgen receptor-dependent gene transcription. In addition, androgen receptor, JMJD2C and LSD1 assemble on chromatin to remove methyl groups from mono, di and trimethylated H3K9. Thus, our data suggest that specific gene regulation requires the assembly and coordinate action of demethylases with distinct substrate specificities. PMID:17277772

Wissmann, Melanie; Yin, Na; Müller, Judith M; Greschik, Holger; Fodor, Barna D; Jenuwein, Thomas; Vogler, Christine; Schneider, Robert; Günther, Thomas; Buettner, Reinhard; Metzger, Eric; Schüle, Roland

2007-02-04

255

Distinct functions of acj6 splice forms in odor receptor gene choice  

PubMed Central

Individual olfactory receptor neurons (ORNs) selectively express one or a small number of odor receptors from among a large receptor repertoire. The expression of an odor receptor dictates the odor response spectrum of the ORN. The process of receptor gene choice relies in part on a combinatorial code of transcription factors. In Drosophila, the POU domain transcription factor Acj6 is one element of the transcription factor code. In acj6 null mutants, many ORNs do not express an appropriate odor receptor gene and thus are not correctly specified. We find that acj6 is alternatively spliced to yield many structurally distinct transcripts in the olfactory organs. We generate flies that express single splice forms of acj6 in an acj6? background. We find that different splice forms are functionally distinct; they differ in their abilities to specify ORN identities. Some individual splice forms can fully rescue the specification of some ORNs. Individual splice forms can function both positively and negatively in receptor gene regulation. ORNs differ in their requirements for splice forms; some are not fully rescued by any single splice form tested, suggesting that some ORNs may require the combinatorial action of multiple splice forms. Late expression of some acj6 splice forms is sufficient to rescue some ORN classes, consistent with a direct role for Acj6 isoforms in receptor gene expression. The results indicate that alternative splicing may add another level of richness to the regulatory code that underlies the process of odor receptor gene choice.

Bai, Lei; Carlson, John R.

2010-01-01

256

Phosphorylated and sumoylation-deficient progesterone receptors drive proliferative gene signatures during breast cancer progression  

PubMed Central

Introduction Progesterone receptors (PR) are emerging as important breast cancer drivers. Phosphorylation events common to breast cancer cells impact PR transcriptional activity, in part by direct phosphorylation. PR-B but not PR-A isoforms are phosphorylated on Ser294 by mitogen activated protein kinase (MAPK) and cyclin dependent kinase 2 (CDK2). Phospho-Ser294 PRs are resistant to ligand-dependent Lys388 SUMOylation (that is, a repressive modification). Antagonism of PR small ubiquitin-like modifier (SUMO)ylation by mitogenic protein kinases suggests a mechanism for derepression (that is, transcriptional activation) of target genes. As a broad range of PR protein expression is observed clinically, a PR gene signature would provide a valuable marker of PR contribution to early breast cancer progression. Methods Global gene expression patterns were measured in T47D and MCF-7 breast cancer cells expressing either wild-type (SUMOylation-capable) or K388R (SUMOylation-deficient) PRs and subjected to pathway analysis. Gene sets were validated by RT-qPCR. Recruitment of coregulators and histone methylation levels were determined by chromatin immunoprecipitation. Changes in cell proliferation and survival were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and western blotting. Finally, human breast tumor cohort datasets were probed to identify PR-associated gene signatures; metagene analysis was employed to define survival rates in patients whose tumors express a PR gene signature. Results 'SUMO-sensitive' PR target genes primarily include genes required for proliferative and pro-survival signaling. DeSUMOylated K388R receptors are preferentially recruited to enhancer regions of derepressed genes (that is, MSX2, RGS2, MAP1A, and PDK4) with the steroid receptor coactivator, CREB-(cAMP-response element-binding protein)-binding protein (CBP), and mixed lineage leukemia 2 (MLL2), a histone methyltransferase mediator of nucleosome remodeling. PR SUMOylation blocks these events, suggesting that SUMO modification of PR prevents interactions with mediators of early chromatin remodeling at 'closed' enhancer regions. SUMO-deficient (phospho-Ser294) PR gene signatures are significantly associated with human epidermal growth factor 2 (ERBB2)-positive luminal breast tumors and predictive of early metastasis and shortened survival. Treatment with antiprogestin or MEK inhibitor abrogated expression of SUMO-sensitive PR target-genes and inhibited proliferation in BT-474 (estrogen receptor (ER)+/PR+/ERBB2+) breast cancer cells. Conclusions We conclude that reversible PR SUMOylation/deSUMOylation profoundly alters target gene selection in breast cancer cells. Phosphorylation-induced PR deSUMOylation favors a permissive chromatin environment via recruitment of CBP and MLL2. Patients whose ER+/PR+ tumors are driven by hyperactive (that is, derepressed) phospho-PRs may benefit from endocrine (antiestrogen) therapies that contain an antiprogestin.

2012-01-01

257

Unusual forms of low density lipoprotein receptors in hamster cell mutants with defects in the receptor structural gene  

PubMed Central

The structure and processing of low density lipoprotein (LDL) receptors in wild-type and LDL receptor-deficient mutant Chinese hamster ovary cells was examined using polyclonal anti-receptor antibodies. As previously reported for human LDL receptors, the LDL receptors in wild- type Chinese hamster ovary cells were synthesized as precursors which were extensively processed by glycosylation to a mature form. In the course of normal receptor turnover, an apparently unglycosylated portion of the cysteine-rich N-terminal LDL binding domain of the receptor is proteolytically removed. The LDL receptor-deficient mutants fall into four complementation groups, ldlA, ldlB, ldlC, and ldlD; results of the analysis of ldlB, ldlC, and ldlD mutants are described in the accompanying paper (Kingsley, D. M., K. F. Kozarsky, M. Segal, and M. Krieger, 1986, J. Cell. Biol, 102:1576-1585). Analysis of ldlA cells has identified three classes of mutant alleles at the ldlA locus: null alleles, alleles that code for normally processed receptors that cannot bind LDL, and alleles that code for abnormally processed receptors. The abnormally processed receptors were continually converted to novel unstable intracellular intermediates. We also identified a compound-heterozygous mutant and a heterozygous revertant which indicate that the ldlA locus is diploid. In conjunction with other genetic and biochemical data, the finding of multiple mutant forms of the LDL receptor in ldlA mutants, some of which appeared together in the same cell, confirm that the ldlA locus is the structural gene for the LDL receptor.

1986-01-01

258

An estrogen-dependent four-gene micronet regulating social recognition: A study with oxytocin and estrogen receptor- and - knockout mice  

Microsoft Academic Search

Estrogens control many physiological and behavioral processes, some of which are connected to reproduction. These include sexual and other social behaviors. Here we implicate four gene products in a micronet required for mammalian social recognition, through which an individual learns to recognize other individuals. Female mice whose genes for the neuropeptide oxytocin (OT) or the estrogen receptor (ER)- or ER-

Elena Choleris; Jan-Åke Gustafsson; Kenneth S. Korach; Louis J. Muglia; Donald W. Pfaff; Sonoko Ogawa

2003-01-01

259

Structural change in dopamine D{sub 2} receptor gene in a patient with neuroleptic malignant syndrome  

SciTech Connect

Dysfunction of the dopaminergic system has been suggested as a pathogenic mechanism in neuroleptic malignant syndrome. Therefore, we examined the complete coding sequences of the dopamine D{sub 2} receptor (DRD2) gene for structural abnormalities in 12 patients with a history of NMS, including two cases of familial NMS. Mutational analysis was performed by denaturing gradient gel electrophoresis (DGGE), a highly sensitive technique for detecting sequence differences. We found in one patient with a history of NMS a nucleotide substitution at codon 310 (CCG{r_arrow}TCG) of exon 7 of the DRD2 gene which predicts the replacement of proline to serine in the third cytoplasmic loop of the receptor, a part of the receptor that interacts with G-proteins. A larger series of patients with NMS needs to be investigated to establish whether this allele is associated with an increased susceptibility to NMS. 25 refs., 1 fig.

Ram, A.; Cao, Q.; Gershon, E.S. [National Institutes of Health, Bethesda, MD (United States)] [and others

1995-06-19

260

Calcitonin gene-related peptide receptors in human gastrointestinal epithelia.  

PubMed Central

1. The secretory responses to calcitonin gene-related peptide (CGRP) receptor agonists have been characterized in two human adenocarcinoma cell lines, namely HCA-7 and Colony-29 (Col-29) epithelia. These cells form polarized epithelial layers when grown on permeable supports and allow changes in electrogenic ion transport in response to agonists to be monitored continuously. 2. alpha-CGRP (rat and human sequences), rat beta-CGRP and human [Tyr0]CGRP applied to the basolateral surface were found to be full agonists, causing prolonged increases in short-circuit current. Concentration-response curves exhibited EC50 values of 0.6-1.5 nM in HCA-7 cells. The same agonists were less effective in Col-29 epithelia, the EC50 values ranging from 1 to 10 nM in these cells. [Cys(ACM)2,7]CGRP was effective in both cell lines and was more potent in HCA-7 cells. 3. CGRP receptors were preferentially located on the basolateral surface in both cell types. Addition of r alpha-CGRP to the apical domain produced significantly smaller secretory responses (8.1% in HCA-7 and 29.2% in Col-29) compared with those produced following basolateral application (100%). 4. In both cell lines r alpha-CGRP-elevated short-circuit current was inhibited by the loop diuretic piretanide (200 microM) and by somatostatin (100 nM). Pretreating epithelia with the cyclo-oxygenase inhibitor, piroxicam (5 microM) had no significant effect upon CGRP responses in either cell line. 5. Rat alpha-CGRP (0.2 nM) responses in HCA-7 epithelia were inhibited by the C-terminal fragment CGRP(8-37) (1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Cox, H M; Tough, I R

1994-01-01

261

Allelic association of human dopamine D sub 2 receptor gene in alcoholism  

SciTech Connect

In a blinded experiment, the authors report the first allelic association of the dopamine D{sub 2} receptor gene in alcoholism. From 70 brain samples of alcoholics and nonalcoholics, DNA was digested with restriction endonucleases and probed with a clone that contained the entire 3{prime} coding exon, the polyadenylation signal, and approximately 16.4 kilobases of noncoding 3{prime} sequence of the human dopamine D{sub 2} receptor gene ({lambda}hD2G1). In the present samples, the presence of A1 allele of the dopamine D{sub 2} receptor gene correctly classified 77% of alcoholics, and its absence classified 72% of nonalcoholics. The polymorphic pattern of this receptor gene suggests that a gene that confers susceptibility to at least one form of alcoholism is located on the q22-q23 region of chromosome 11.

Blum, K.; Sheridan, P.J.; Montgomery, A.; Jagadeeswaran, P.; Nogami, H.; Briggs, A.H. (Univ. of Texas Health Science Center, San Antonio (USA)); Noble, E.P.; Ritchie, T.; Cohn, J.B. (Univ. of California, Los Angeles (USA))

1990-04-18

262

Life stress and diminished expression of genes encoding glucocorticoid receptor and 2-adrenergic receptor in children with asthma  

Microsoft Academic Search

Despite evidence that stressful experience can exacerbate the symptoms of asthma, little is known about the biological mechanisms through which this occurs. This study examined whether life stress reduces expression of the genes coding for the glucocorticoid receptor and the 2-adrenergic receptor. A total of 77 children were enrolled in the study (59% male; mean age, 13.5 years). Thirty-nine of

Gregory E. Miller; Edith Chen

2006-01-01

263

Androgen receptor gene polymorphisms and alterations in prostate cancer: of humanized mice and men.  

PubMed

Germline polymorphisms and somatic mutations of the androgen receptor (AR) have been intensely investigated in prostate cancer but even with genomic approaches their impact remains controversial. To assess the functional significance of AR genetic variation, we converted the mouse gene to the human sequence by germline recombination and engineered alleles to query the role of a polymorphic glutamine (Q) tract implicated in cancer risk. In a prostate cancer model, AR Q tract length influences progression and castration response. Mutation profiling in mice provides direct evidence that somatic AR variants are selected by therapy, a finding validated in human metastases from distinct treatment groups. Mutant ARs exploit multiple mechanisms to resist hormone ablation, including alterations in ligand specificity, target gene selectivity, chaperone interaction and nuclear localization. Regardless of their frequency, these variants permute normal function to reveal novel means to target wild type AR and its key interacting partners. PMID:21689727

Robins, Diane M

2011-06-12

264

Evolutionary History and Functional Characterization of Androgen Receptor Genes in Jawed Vertebrates  

PubMed Central

Vertebrates show diverse sexual characters in sexually attractive and reproductive organs, which are regulated by steroid hormones, particularly androgens. However, the evolutionary history of androgen receptor (AR) gene remains largely unknown on the basis of phylogenic and functional analyses. To elucidate the evolutionary history and functional diversification of AR genes in vertebrates, we cloned the AR cDNAs from a shark, basal ray-finned fishes (Actinopterygii), namely bichir and sturgeon (Acipenseriformes), and teleosts including a basal teleost, arowana (Osteoglossiformes). Molecular phylogenetic analysis revealed that the gene duplication event that gave rise to two different teleost ARs (? and ?) likely occurred in the actinopterygian lineage leading to teleosts after the divergence of Acipenseriformes but before the split of Osteoglossiformes, which is compatible with the phylogenetic timing of teleost-specific genome duplication. Searching for AR genes in the medaka genome indicated that the teleost AR gene duplication has been associated with the duplication between chromosomes 10 and 14. Our functional analysis revealed that the shark AR activates the target gene via androgen response element by classical androgens. The teleost AR? showed the unique intracellular localization with a significantly higher transactivating capacity than that by teleost AR?. These findings indicate that the most ancient type of AR, as activated by the classical androgens as ligands, emerged before the Chondrichthyes-Osteichthyes split, and the AR gene was duplicated during the teleost-specific genome duplication event. We report here for the first time the accurate evolutionary history of AR gene and functional characterization of AR duplicates in teleost lineage.

Ogino, Yukiko; Katoh, Hironori; Kuraku, Shigehiro; Yamada, Gen

2009-01-01

265

Hormone receptor-related gene polymorphisms and prostate cancer risk in North Indian population.  

PubMed

The purpose of this study was to analyse the frequency and type of mutations in the coding region of androgen receptor (AR) and to determine the role of polymorphisms in the intron 1 of ERalpha, exon 5 of ERbeta, intron 7 of progesterone, exon 7 of the aromatase (CYP19) and exon 9 of VDR genes in the risk of prostate cancer. PCR-RFLP analysis of all above the genes was on 100 prostate cancer patients and an equal number of matching controls. The study also included PCR-SSCP analyses of exons 2-8 of AR gene. The genotype containing -/- allele of ERalpha gene was statistically significant for the risk of prostate cancer pose (OR, 2.70; 95% CI, 1.08-6.70, P = 0.032) Rr genotype of ERbeta gene also have a higher risk (OR, 1.65; 95% CI, 0.52-5.23) for prostate cancer. The Cys allele of CYP19 gene was also associated with statistically significant increased risk of prostate cancer (OR; 2.28, 95% CI, 1.20-4.35, P = 0.012). tt genotype of codon 352 of VDR gene showed an OR of 0.43 for (95% CI, 0.13-1.39) and an OR for Tt genotype was 0.65 (95% CI, 0.36-1.16). Taken together, the results showed that in North Indian population, ERalpha and CYP19 genes may be playing a role in the risk of prostate cancer. PMID:18483761

Onsory, Khadijeh; Sobti, R C; Al-Badran, Adnan Issa; Watanabe, Masatoshi; Shiraishi, Taizo; Krishan, Awtar; Mohan, Harsh; Kaur, Pushpinder

2008-05-16

266

Differential gene expression in mouse primary hepatocytes exposed to the peroxisome proliferator-activated receptor ? agonists  

PubMed Central

Background Fibrates are a unique hypolipidemic drugs that lower plasma triglyceride and cholesterol levels through their action as peroxisome proliferator-activated receptor alpha (PPAR?) agonists. The activation of PPAR? leads to a cascade of events that result in the pharmacological (hypolipidemic) and adverse (carcinogenic) effects in rodent liver. Results To understand the molecular mechanisms responsible for the pleiotropic effects of PPAR? agonists, we treated mouse primary hepatocytes with three PPAR? agonists (bezafibrate, fenofibrate, and WY-14,643) at multiple concentrations (0, 10, 30, and 100 ?M) for 24 hours. When primary hepatocytes were exposed to these agents, transactivation of PPAR? was elevated as measured by luciferase assay. Global gene expression profiles in response to PPAR? agonists were obtained by microarray analysis. Among differentially expressed genes (DEGs), there were 4, 8, and 21 genes commonly regulated by bezafibrate, fenofibrate, and WY-14,643 treatments across 3 doses, respectively, in a dose-dependent manner. Treatments with 100 ?M of bezafibrate, fenofibrate, and WY-14,643 resulted in 151, 149, and 145 genes altered, respectively. Among them, 121 genes were commonly regulated by at least two drugs. Many genes are involved in fatty acid metabolism including oxidative reaction. Some of the gene changes were associated with production of reactive oxygen species, cell proliferation of peroxisomes, and hepatic disorders. In addition, 11 genes related to the development of liver cancer were observed. Conclusion Our results suggest that treatment of PPAR? agonists results in the production of oxidative stress and increased peroxisome proliferation, thus providing a better understanding of mechanisms underlying PPAR? agonist-induced hepatic disorders and hepatocarcinomas.

Guo, Lei; Fang, Hong; Collins, Jim; Fan, Xiao-hui; Dial, Stacey; Wong, Alex; Mehta, Kshama; Blann, Ernice; Shi, Leming; Tong, Weida; Dragan, Yvonne P

2006-01-01

267

Direct downstream targets of proneural activators in the imaginal disc include genes involved in lateral inhibitory signaling.  

PubMed

In Drosophila imaginal discs, the spatially restricted activities of the achaete (ac) and scute (sc) proteins, which are transcriptional activators of the basic-helix-loop-helix class, define proneural clusters (PNCs) of potential sensory organ precursor (SOP) cells. Here, we report the identification of several genes that are direct downstream targets of ac-sc activation, as judged by the following criteria. The genes are expressed in the PNCs of the wing imaginal disc in an ac-sc-dependent manner; the proximal promoter regions of all of these genes contain one or two high-affinity ac-sc binding sites, which define the novel consensus GCAGGTG(T/G)NNNYY; where tested, these binding sites are required in vivo for PNC expression of promoter-reporter fusion genes. Interestingly, these ac-sc target genes, including Bearded, Enhancer of split m7, Enhancer of split m8, and scabrous, are all known or believed to function in the selection of a single SOP from each PNC, a process mediated by inhibitory cell-cell interactions. Thus, one of the earliest steps in adult peripheral neurogenesis is the direct activation by proneural proteins of genes involved in restricting the expression of the SOP cell fate. PMID:7958878

Singson, A; Leviten, M W; Bang, A G; Hua, X H; Posakony, J W

1994-09-01

268

Toll-like receptor gene polymorphisms are associated with susceptibility to graves' ophthalmopathy in Taiwan males  

PubMed Central

Background Toll-like receptors (TLRs) are a family of pattern-recognition receptors, which plays a role in eliciting innate/adaptive immune responses and developing chronic inflammation. The polymorphisms of TLRs have been associated with the risk of various autoimmune diseases, including systemic lupus erythematosus (SLE), multiple sclerosis and rheumatorid arthritis. The aim of this study was to evaluate whether TLR genes could be used as genetic markers for the development of Graves' ophthalmopathy (GO). Methods 6 TLR-4 and 2 TLR-9 gene polymorphisms in 471 GD patients (200 patients with GO and 271 patients without GO) from a Taiwan Chinese population were evaluated. Results No statistically significant difference was observed in the genotypic and allelic frequencies of TLR-4 and TLR-9 gene polymorphisms between the GD patients with and without GO. However, sex-stratified analyses showed that the association between TLR-9 gene polymorphism and GO phenotype was more pronounced in the male patients. The odds ratios (ORs) was 2.11 (95% confidence interval [CI] = 1.14-3.91) for rs187084 AàG polymorphism and 1.97 (95% CI = 1.07-3.62) for rs352140 AàG polymorphism among the male patients. Increasing one G allele of rs287084 and one A allele of rs352140 increased the risk of GO (p values for trend tests were 0.0195 and 0.0345, respectively). Further, in haplotype analyses, the male patients carrying the GA haplotype had a higher risk of GO (odds ratio [OR] = 2.02, 95% confidence interval [CI] = 1.09-3.73) than those not carrying the GA haplotype. Conclusion The present data suggest that TLR-9 gene polymorphisms were significantly associated with increased susceptibility of ophthalmopathy in male GD patients.

2010-01-01

269

PLK1 signaling in breast cancer cells cooperates with estrogen receptor-dependent gene transcription.  

PubMed

Polo-like kinase 1 (PLK1) is a key regulator of cell division and is overexpressed in many types of human cancers. Compared to its well-characterized role in mitosis, little is known about PLK1 functions in interphase. Here, we report that PLK1 mediates estrogen receptor (ER)-regulated gene transcription in human breast cancer cells. PLK1 interacts with ER and is recruited to ER cis-elements on chromatin. PLK1-coactivated genes included classical ER target genes such as Ps2, Wisp2, and Serpina3 and were enriched in developmental and tumor-suppressive functions. Performing large-scale phosphoproteomics of estradiol-treated MCF7 cells in the presence or absence of the specific PLK1 inhibitor BI2536, we identified several PLK1 end targets involved in transcription, including the histone H3K4 trimethylase MLL2, the function of which on ER target genes was impaired by PLK1 inhibition. Our results propose a mechanism for the tumor-suppressive role of PLK1 in mammals as an interphase transcriptional regulator. PMID:23770244

Wierer, Michael; Verde, Gaetano; Pisano, Paola; Molina, Henrik; Font-Mateu, Jofre; Di Croce, Luciano; Beato, Miguel

2013-06-13

270

Structure and variation of three canine genes involved in serotonin binding and transport: the serotonin receptor 1A gene (htr 1A), serotonin receptor 2A gene (htr 2A), and serotonin transporter gene (slc6A4)  

Microsoft Academic Search

Aggressive behavior is the most frequently encountered behavioral problem in dogs. Abnormalities in brain serotonin me- tabolism have been described in aggressive dogs. We studied canine serotonergic genes to investigate genetic factors un- derlying canine aggression. Here, we describe the characterization of three genes of the canine serotonergic system: the serotonin receptor 1A and 2A gene (htr1A and htr2A) and

L. van den Berg; L. Kwant; M. S. Hestand; B. A. van Oost; P. A. J. Leegwater

2005-01-01

271

Association of the dopamine receptor interacting protein gene, NEF3, with early response to antipsychotic medication.  

PubMed

Genetic variation in antipsychotic drug targets could underlie variability among patients in the time required for antipsychotic effects to be elicited. In a clinical, pharmacogenetic study we focused on the dopamine receptor interacting protein (DRIP) gene family. DRIPs are pivotally involved in regulating dopamine receptor signal transduction. Consecutively hospitalized, acutely psychotic patients with DSM-IV schizophrenia (n=121) were included in the study if they received treatment with typical antipsychotic medication (TYP, n=72) or TYP plus risperidone (TYP-R, n=49) for at least 2 wk. Clinical state and adverse effects were rated at baseline and after 2 wk. Patients improved significantly on both TYP and TYP-R with no significant difference between them. Early responders were defined as patients whose PANSS change scores were greater than the median. Twenty-two single nucleotide polymorphisms (SNPs) were analysed in five DRIP-encoding genes. Two SNPs in NEF3, which encodes the DRIP, neurofilament-medium (NF-M), were associated with early response (rs1457266, p=0.01; rs1379357, p=0.006). A 5 SNP haplotype spanning NEF3 was over-represented in early responders (p=0.015), in the combined patient group and in the TYP group alone. These findings suggest that variation in NEF3, most likely functional variants that are in linkage disequilibrium with the SNPs that we studied, influences rate of response to TYP. Since NEF3 is primarily associated with dopamine D1 receptor function, the evidence for a complementary role of dopamine D1 receptors in antipsychotic effects is considered. The findings reported here open an interesting research avenue in the pharmacogenetics of antipsychotic effects but require replication in larger samples treated in a controlled context. PMID:16734940

Strous, Rael D; Greenbaum, Lior; Kanyas, Kyra; Merbl, Yifat; Horowitz, Anat; Karni, Osnat; Viglin, Dina; Olender, Tsviya; Deshpande, Smita N; Lancet, Doron; Ben-Asher, Edna; Lerer, Bernard

2006-05-31

272

Epidermal growth factor receptor gene amplification in atypical adenomatous hyperplasia of the lung  

PubMed Central

Atypical adenomatous hyperplasia (AAH) is postulated to be the earliest morphologic precursor lesion in lung carcinogenesis. The epidermal growth factor receptor (EGFR), one of the members of the Erb-2 family of receptors, is commonly expressed in non-small cell lung carcinoma (NSCLC). A subset of the patients with NSCLC has molecular abnormalities in the EGFR gene, including missense mutations and deletions and/or abnormal gene copy numbers, and the relative importance of each of these for patient outcome is an area of great interest. Recent reports show that EGFR mutations are rare or absent in AAH and are rare in bronchioloalveolar carcinoma (BAC). However, the EGFR gene copy number status in AAH is unknown. In this study, we examined the EGFR gene copy number status in lung adenocarcinomas, synchronous AAH, and BAC in surgical pathology resection specimens. EGFR gene copy number was analyzed by chromogenic in situ hybridization (CISH) using formalin fixed paraffin embedded tissue sections and EGFR probes as recommended by the manufacturer. A known positive case of high-grade glioma was used as a positive control. The results indicate that four of eight adenocarcinomas (50%) had more than five EGFR signals per nucleus, suggesting a gain in copy number. Interestingly, in four of nine cases of AAH (44.4%) more than three EGFR signals per nucleus were noted, with scattered cells showing up to 6 signals per nucleus. In addition, in five of 12 cases of BAC (42%), more than three EGFR signals per nucleus were noted. In the remaining cases two to three intranuclear dot-like peroxidase positive signals were present consistent with non-amplification of the gene. Our study reveals an abnormal EGFR gene copy gain in several cases of AAH. In our cohort, the rate of EGFR gene copy abnormalities in AAH appears similar to BAC and lower than in lung adenocarcinomas. These findings suggest that although EGFR gene copy abnormalities may be an early event in lung carcinogenesis, they are associated with tumor progression to invasive cancer and highlight the complexity of tumor morphogenesis.

McIntire, Maria G; Santagata, Sandro; Ligon, Keith; Chirieac, Lucian R

2010-01-01

273

Epigenetic regulation of olfactory receptor gene expression by the Myb-MuvB/dREAM complex  

PubMed Central

In both mammals and insects, an olfactory neuron will usually select a single olfactory receptor and repress remaining members of large receptor families. Here we show that a conserved multiprotein complex, Myb–MuvB (MMB)/dREAM, plays an important role in mediating neuron-specific expression of the carbon dioxide (CO2) receptor genes (Gr63a/Gr21a) in Drosophila. Activity of Myb in the complex is required for expression of Gr63a/Gr21a and acts in opposition to the histone methyltransferase Su(var)3-9. Consistent with this, we observed repressive dimethylated H3K9 modifications at the receptor gene loci, suggesting a mechanism for silencing receptor gene expression. Conversely, other complex members, Mip120 (Myb-interacting protein 120) and E2F2, are required for repression of Gr63a in inappropriate neurons. Misexpression in mutants is accompanied by an increase in the H3K4me3 mark of active chromatin at the receptor gene locus. Nuclei of CO2 receptor-expressing neurons contain reduced levels of the repressive subunit Mip120 compared with surrounding neurons and increased levels of Myb, suggesting that activity of the complex can be regulated in a cell-specific manner. Our evidence suggests a model in which olfactory receptors are regulated epigenetically and the MMB/dREAM complex plays a critical role in specifying, maintaining, and modulating the receptor-to-neuron map.

Sim, Choon Kiat; Perry, Sarah; Tharadra, Sana Khalid; Lipsick, Joseph S.; Ray, Anandasankar

2012-01-01

274

Molecular cloning and chromosomal localization of one of the human glutamate receptor genes  

SciTech Connect

Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are classified on the basis of their activation by different agonists. The agonists kainate and {alpha}-amino-3-hydroxy-5-methyl-4-isoxasolepropionic acid define a class of glutamate receptors termed kainate receptors. The authors have isolated and sequenced a human glutamate receptor (GluHI) cDNA and determined the chromosomal localization of its gene. The DNA sequence of GluHI would encode a 907-amino acid protein that has a 97% identity to one of the rodent kainate receptor subunits. Many of the changes between the predicted amino acid sequence of GluHI and the most similar rodent kainate receptor (GluRI) occur in a region of the protein encoded in rodents by an alternatively spliced exon. The extreme conservation between the human and rat kainate receptor subunits suggests that a similar gene family will encode human kainate receptors. The GluHI mRNA is widely expressed in human brain. The human gene encoding the GluHI subunit is located at 5q33. While the GluHI gene is not located near a chromosomal region associated with any human neurogenetic disorders, the homologous region on mouse chromosome 11 contains the sites of five neurologic mutations.

Puckett, C.; Gomez, C.M.; Tung, H.; Meier, T.J.; Hood, L. (California Inst. of Technology, Pasadena (United States)); Korenberg, J.R.; Xiao Ning Chen (Cedar Sinai Medical Center, Los Angeles, CA (United States))

1991-09-01

275

Epigenetic regulation of olfactory receptor gene expression by the Myb-MuvB/dREAM complex.  

PubMed

In both mammals and insects, an olfactory neuron will usually select a single olfactory receptor and repress remaining members of large receptor families. Here we show that a conserved multiprotein complex, Myb-MuvB (MMB)/dREAM, plays an important role in mediating neuron-specific expression of the carbon dioxide (CO(2)) receptor genes (Gr63a/Gr21a) in Drosophila. Activity of Myb in the complex is required for expression of Gr63a/Gr21a and acts in opposition to the histone methyltransferase Su(var)3-9. Consistent with this, we observed repressive dimethylated H3K9 modifications at the receptor gene loci, suggesting a mechanism for silencing receptor gene expression. Conversely, other complex members, Mip120 (Myb-interacting protein 120) and E2F2, are required for repression of Gr63a in inappropriate neurons. Misexpression in mutants is accompanied by an increase in the H3K4me3 mark of active chromatin at the receptor gene locus. Nuclei of CO(2) receptor-expressing neurons contain reduced levels of the repressive subunit Mip120 compared with surrounding neurons and increased levels of Myb, suggesting that activity of the complex can be regulated in a cell-specific manner. Our evidence suggests a model in which olfactory receptors are regulated epigenetically and the MMB/dREAM complex plays a critical role in specifying, maintaining, and modulating the receptor-to-neuron map. PMID:23105004

Sim, Choon Kiat; Perry, Sarah; Tharadra, Sana Khalid; Lipsick, Joseph S; Ray, Anandasankar

2012-10-26

276

Gene Regulation by Retinoid Receptors in Human Mammary Epithelial Cells.  

National Technical Information Service (NTIS)

Based on Preliminary Data, we hypothesized that loss of retinoic acid receptor function might promote dysregulated growth and loss of epithelial polarity. We now report that retinoids and the retinoic acid receptor-beta are important regulators of prolife...

V. L. Seewaldt

2003-01-01

277

A novel human gene encoding a G-protein-coupled receptor (GPR15) is located on chromosome 3  

SciTech Connect

We used sequence similarities among G-protein-coupled receptor genes to discover a novel receptor gene. Using primers based on conserved regions of the opioid-related receptors, we isolated a PCR product that was used to locate the full-length coding region of a novel human receptor gene, which we have named GPR15. A comparison of the amino acid sequence of the receptor gene, which we have named GPR15. A comparison of the amino acid sequence of the receptor encoded by GPR15 with other receptors revealed that it shared sequence identity with the angiotensin II AT1 and AT2 receptors, the interleukin 8b receptor, and the orphan receptors GPR1 and AGTL1. GPR15 was mapped to human chromosome 3q11.2-q13.1. 12 refs., 2 figs.

Heiber, M.; Marchese, A.; O`Dowd, B.F. [Univ. of Toronto, Ontario (Canada)] [and others

1996-03-05

278

Chromosomal gene organization of the human granulocyte colony-stimulating factor receptor  

SciTech Connect

The human chromosomal gene for the granulocyte CSF (G-CSF) receptor was molecularly cloned from a human gene library. The gene is about 16.5 kb long, and present in a single copy per haploid human genome. The human G-CSF receptor gene consists of 17 exons, and the sequences of exons are completely identical to those of cDNAs isolated from human U-937 myeloid leukemia or placenta cDNA libraries. The G-CSF receptor can be subdivided into several regions: an Ig-like domain, a cytokine receptor homologous domain, three fibronectin type III domains, a transmembrane domain, and a cytoplasmic region. Exons 3-17 code for the G-CSF receptor protein, and each subdomain of the receptor is encoded by a set of exons. Primer extension analysis of the G-CSF receptor mRNA identified major and minor transcription start sites. There is no canonical [open quotes]TATA[close quotes] box upstream of the CAP site. About 110 nucleotides upstream of the transcription initiation site of the gene, there is an element of 18 nucleotides that is homologous to the sequences found in the promoter of human myeloperoxidase and neutrophil elastase genes. 38 refs., 7 figs.

Seto, Yoshiyuki; Fukunaga, Rikiro; Nagata, Shigekazu (Osaka Bioscience Institute (Japan))

1992-01-01

279

Association study of dopamine D3 receptor gene and schizophrenia.  

PubMed

Several groups have reported an association between schizophrenia and the MscI polymorphism in the first exon of the dopamine D3 receptor gene (DRD3). We studied this polymorphism using a North American sample (117 patients plus 188 controls) and an Italian sample (97 patients plus 64 controls). In the first part of the study, we compared allele frequencies of schizophrenia patients and unmatched controls and observed a significant difference in the total sample (P = 0.01). The second part of the study involved a case control approach in which each schizophrenia patient was matched to a control of the same sex, and of similar age and ethnic background. The DRD3 allele frequencies of patients and controls revealed no significant difference between the two groups in the Italian (N = 53) or the North American (N = 54) matched populations; however, when these two matched samples were combined, a significant difference was observed (P = 0.026). Our results suggest that the MscI polymorphism may be associated with schizophrenia in the populations studied. PMID:8825896

Kennedy, J L; Billett, E A; Macciardi, F M; Verga, M; Parsons, T J; Meltzer, H Y; Lieberman, J; Buchanan, J A

1995-12-18

280

Maternal Undernourished Fetal Kidneys Exhibit Differential Regulation of Nephrogenic Genes Including Downregulation of the Notch Signaling Pathway  

PubMed Central

Maternal undernutrition results in offspring nephron number reduction and hypertension that are hypothesized to begin as compensatory changes in fetal gene expression during gestation. To evaluate mechanisms of dysregulated nephrogenesis, pregnant Sprague Dawley rats were 50% food restricted from embryonic day (E) 10 to E20. At E20, fetal male kidneys were examined by microarray analysis. A total of 476 differentially expressed transcripts were detected including those regulating development and differentiation, mitosis and cell cycle, chromatin assembly, and steroid hormone regulation. Differentially regulated genes were detected in MAPK/ERK, Wnt, and Notch signaling pathways. Validation of the microarray results was performed for the Notch signaling pathway, an important pathway in nephron formation. Protein expression of Notch pathway factors by Western blotting showed significantly decreased Notch2 and downstream effector Hey1 protein expression, while Ctbp1 co-repressor was increased. These data together show that maternal undernutrition results in developmental disruption in fetal nephrogenesis gene expression signaling.

Magee, Thomas R.; Tafti, Sanaz A.; Desai, Mina; Liu, Qinghai; Ross, Michael G.; Nast, Cynthia C

2011-01-01

281

Maternal undernourished fetal kidneys exhibit differential regulation of nephrogenic genes including downregulation of the Notch signaling pathway.  

PubMed

Maternal undernutrition results in offspring nephron number reduction and hypertension that are hypothesized to begin as compensatory changes in fetal gene expression during gestation. To evaluate mechanisms of dysregulated nephrogenesis, pregnant Sprague Dawley rats were 50% food restricted from embryonic day (E) 10 to E20. At E20, fetal male kidneys were examined by microarray analysis. A total of 476 differentially expressed transcripts were detected including those regulating development and differentiation, mitosis and cell cycle, chromatin assembly, and steroid hormone regulation. Differentially regulated genes were detected in MAPK/ERK, Wnt, and Notch signaling pathways. Validation of the microarray results was performed for the Notch signaling pathway, an important pathway in nephron formation. Protein expression of Notch pathway factors by Western blotting showed significantly decreased Notch2 and downstream effector Hey1 protein expression, while Ctbp1 co-repressor was increased. These data together show that maternal undernutrition results in developmental disruption in fetal nephrogenesis gene expression signaling. PMID:21273641

Magee, Thomas R; Tafti, Sanaz A; Desai, Mina; Liu, Qinghai; Ross, Michael G; Nast, Cynthia C

2011-01-27

282

Association of bovine meat quality traits with genes included in the PPARG and PPARGC1A networks.  

PubMed

Understanding which are the genetic variants underlying the nutritional and sensory properties of beef, enables improvement in meat quality. The aim of this study is to identify new molecular markers for meat quality through an association study using candidate genes included in the PPARG and PPARGC1A networks given their master role in coordinating metabolic adaptation in fat tissue, muscle and liver. Amongst the novel associations found in this study, selection of the positive marker variants of genes such as BCL3, LPL, PPARG, SCAP, and SCD will improve meat organoleptic characteristics and health by balancing the n-6 to n-3 fatty acid ratio in meat. Also previous results on GDF8 and DGAT1 were validated, and the novel ATF4, HNF4A and PPARGC1A associations, although slightly under the significance threshold, are consistent with their physiological roles. These data contribute insights into the complex gene-networks underlying economically important traits. PMID:23567132

Sevane, N; Armstrong, E; Cortés, O; Wiener, P; Wong, R Pong; Dunner, S

2013-03-01

283

Detection of clonal lymphoid receptor gene rearrangements in langerhans cell histiocytosis.  

PubMed

Langerhans cell histiocytosis (LCH), also known as histiocytosis X, is a rare human disorder characterized by an abnormal accumulation and/or clonal proliferation of Langerhans cells (LCs) in various body organs. The cellular origin of LCs has been a subject of considerable debate since their discovery. As specialized dendritic cells strategically located in epithelia, LCs are generally considered to be of myeloid origin from the bone marrow, however, recent studies in mice have shown that LCs can be derived from lymphoid-committed CD4 precursors, suggesting a lymphoid origin. In human LCH, concomitant or sequential occurrence of a lymphoid or myeloid malignancy has been occasionally reported, suggesting the presence of lineage plasticity and/or the possibility of transdifferentiation of 2 otherwise morphologically and immunophenotypically different neoplasms. To gain a better understanding of the pathogenesis and cellular origin of human LCH, we retrospectively investigated 46 well-characterized LCH cases to detect clonal rearrangements of T-cell receptor gamma gene (TRG@) and immunoglobulin heavy chain and kappa light chain genes (IGH@/IGK@). The study included 25 males and 21 females, with ages ranging from <1 to 59 years. None (0/46) of the cases had a known history or concurrent B or T-cell lymphoma. Of 46 cases, 30% (14/46) cases had clonal IGH@ (4 cases), IGK@ (5 cases) or TRG@ (9 cases) gene rearrangements, respectively. Interestingly, of the 14 cases with at least one clonal rearrangement of lymphoid receptor genes, 3 LCH cases were shown to have both TRG@ and IGH@/IGK@ gene rearrangements, but failed to express T-cell or B-cell lineage specific or associated markers, suggesting lineage plasticity or infidelity of the neoplasm. Furthermore, all of the 14 cases were negative for t(14;18) by quantitative PCR analysis. In conclusion, our study shows that lymphoid receptor gene rearrangements can be detected in a subset of sporadic LCH cases, suggesting a possible lineage relationship between LCs and lymphoid cells or alternatively, derivation of LCs from lymphoid/myeloid precursors. The results provide genotypic evidence supporting the current notion of lineage plasticity of hematopoietic cells and their associated neoplasms. PMID:20551822

Chen, Wei; Wang, Jun; Wang, Endi; Lu, Ying; Lau, Sean K; Weiss, Lawrence M; Huang, Qin

2010-07-01

284

Molecular characterization of the leptin receptor gene as a candidate gene in the pulmonary hypertension syndrome in broiler chickens.  

PubMed

Leptin Receptor Gene (LEPR) is a candidate gene in understanding the genetic basis of the Pulmonary Hypertension Syndrome (PHS) in broilers. Identification and evaluation of genetic polymorphisms in LEPR may provide a link between traits like Body Weight (BW) and Total Ventricle weight (TV) to the development of PHS. In this study, primers were designed in exons, upstream and downstream sequences to identify mutations in the LEPR on four broilers selected with respect to the PHS-related traits. About 77% of the 11,820 bp of the LEPR gene covered by the primers were sequenced. No mutations were found between the chickens associating the traits to the occurrence of PHS. However, 42 single nucleotide polymorphisms and four Indels were found between the reference sequences of the red jungle fowl and the experimental population. Ten of these mutations were not previously reported in LEPR at the genomic and transcript sequences (NP_989654.1, ENSGALT00000018009). The 10 mutations include six SNPs in intron regions, two Indels and two non-synonymous SNPs. The two new non-synonymous SNPs; G301A and A1637G, led to amino acid change A89T and N534S, respectively. PMID:23755410

Bamidele, O; Van As, P; Elferink, M G

2012-12-15

285

Differential gene body methylation and reduced expression of cell adhesion and neurotransmitter receptor genes in adverse maternal environment.  

PubMed

Early life adversity, including adverse gestational and postpartum maternal environment, is a contributing factor in the development of autism, attention deficit hyperactivity disorder (ADHD), anxiety and depression but little is known about the underlying molecular mechanism. In a model of gestational maternal adversity that leads to innate anxiety, increased stress reactivity and impaired vocal communication in the offspring, we asked if a specific DNA methylation signature is associated with the emergence of the behavioral phenotype. Genome-wide DNA methylation analyses identified 2.3% of CpGs as differentially methylated (that is, differentially methylated sites, DMSs) by the adverse environment in ventral-hippocampal granule cells, neurons that can be linked to the anxiety phenotype. DMSs were typically clustered and these clusters were preferentially located at gene bodies. Although CpGs are typically either highly methylated or unmethylated, DMSs had an intermediate (20-80%) methylation level that may contribute to their sensitivity to environmental adversity. The adverse maternal environment resulted in either hyper or hypomethylation at DMSs. Clusters of DMSs were enriched in genes that encode cell adhesion molecules and neurotransmitter receptors; some of which were also downregulated, indicating multiple functional deficits at the synapse in adversity. Pharmacological and genetic evidence links many of these genes to anxiety. PMID:23340501

Oh, J-E; Chambwe, N; Klein, S; Gal, J; Andrews, S; Gleason, G; Shaknovich, R; Melnick, A; Campagne, F; Toth, M

2013-01-22

286

Increased expression of the epidermal growth factor receptor gene in malignant gliomas is invariably associated with gene amplification  

Microsoft Academic Search

Primary malignant gliomas from 63 patients were analyzed to determine the relationship between amplification of the gene encoding the epidermal growth factor receptor (EGFR) and expression of the corresponding mRNA. Twenty-four tumors were found to have amplified the EGFR gene and amplification of other genes occurred in three additional tumors. Hybridization with synthetic RNA probes was used to quantitate mRNA

A. J. Wong; S. H. Bigner; D. D. Bigner; K. W. Kinzler; S. R. Hamilton; B. Vogelstein

1987-01-01

287

Identification and characterization of human taste receptor genes belonging to the TAS2R family  

Microsoft Academic Search

The sense of taste is a chemosensory system responsible for basic food appraisal. Humans distinguish between five primary tastes: bitter, sweet, sour, salty and umami. The molecular events in the perception of bitter taste are believed to start with the binding of specific water-soluble molecules to G-protein-coupled receptors encoded by the TAS2R\\/T2R family of taste receptor genes. TAS2R receptors are

C. Conte; M. Ebeling; A. Marcuz; P. Nef; P. J. Andres-Barquin

2002-01-01

288

Expression of members of the putative olfactory receptor gene family in mammalian germ cells  

Microsoft Academic Search

A SERIES of genomic and complementary DNA clones encoding new putative members of G protein-coupled receptors were isolated using homology cloning and low-stringency polymerase chain reaction1,2. Among the unidentified receptors ('orphan receptors'), a human genomic clone (HGMP07) was characterized by the presence of its transcripts in the testis and by its belonging to a large subfamily of genes sharing extensive

Marc Parmentier; Frédéric Libert; Stéphane Schurmans; Serge Schiffmann; Anne Lefort; Dominique Eggerickx; Catherine Ledent; Catherine Mollereau; Catherine Gérard; Jason Perret; Anton Grootegoed; Gilbert Vassart

1992-01-01

289

Linkage of M5 Muscarinic and ?7Nicotinic Receptor Genes on 15q13 to Schizophrenia  

Microsoft Academic Search

Most antipsychotic drugs act on the forebrain by blocking dopamine receptors. In rodents, the M5 muscarinic receptor (CHRM5) is important for prolonged dopamine release. We typed polymorphisms in CHRM5 and ?7-nicotinic receptor (CHRNA7) genes on 15q13 in 82 Canadian families having at least 1 schizophrenic patient. Using the Family-Based Association Test, we performed haplotype analysis of the 2 loci and

Vincenzo De Luca; Haoran Wang; Alessio Squassina; Greg W. H. Wong; John Yeomans; James L. Kennedy

2004-01-01

290

Estrogen-related receptor ? modulates the expression of adipogenesis-related genes during adipocyte differentiation  

Microsoft Academic Search

Estrogen-related receptor ? (ERR?) is an orphan nuclear receptor that regulates cellular energy metabolism by modulating gene expression involved in fatty acid oxidation and mitochondrial biogenesis in brown adipose tissue. However, the physiological role of ERR? in adipogenesis and white adipose tissue development has not been well studied. Here, we show that ERR? and ERR?-related transcriptional coactivators, peroxisome proliferator-activated receptor

Nobuhiro Ijichi; Kazuhiro Ikeda; Kuniko Horie-Inoue; Ken Yagi; Yasushi Okazaki; Satoshi. Inoue

2007-01-01

291

Deficient pheromone responses in mice lacking a cluster of vomeronasal receptor genes  

Microsoft Academic Search

The mammalian vomeronasal organ (VNO), a part of the olfactory system, detects pheromones-chemical signals that modulate social and reproductive behaviours. But the molecular receptors in the VNO that detect these chemosensory stimuli remain undefined. Candidate pheromone receptors are encoded by two distinct and complex superfamilies of genes, V1r and V2r (refs 3 and 4), which code for receptors with seven

Karina Del Punta; Trese Leinders-Zufall; Ivan Rodriguez; David Jukam; Charles J. Wysocki; Sonoko Ogawa; Frank Zufall; Peter Mombaerts

2002-01-01

292

?2Adrenergic receptor gene variants and risk for autism in the AGRE cohort  

Microsoft Academic Search

The ?2-adrenergic receptor is part of the catecholamine system, and variants at two polymorphic sites in the gene coding for the receptor (ADRB2) confer increased activity. Overstimulation of this receptor may alter brain development, and has been linked to autism in non-identical twins. The objective of this study was to determine whether alleles in ADRB2 are associated with diagnosis of

K Cheslack-Postava; M D Fallin; D Avramopoulos; S L Connors; A W Zimmerman; C G Eberhart; C J Newschaffer

2007-01-01

293

Glucocorticoid-enhanced expression of dioxin target genes through regulation of the rat aryl hydrocarbon receptor  

Microsoft Academic Search

The aryl hydrocarbon receptor (AhR) and glucocorticoid receptor (GR) are ligand-activated transcription factors and members of the basic helix-loop-helix Period-aryl hydrocarbon nuclear translocator-single minded and nuclear hormone receptor superfamilies, respectively. Besides their individual role as acti- vators of specific gene transcription, also interplay between both transcription factors can be an important mechanism of regula- tion. In this study, we report

Edwin Sonneveld; Arjen Jonas; Onno C. Meijer; Abraham Brouwer; Bart van der Burg

2007-01-01

294

Sequence, genetic analysis, and expression of Actinobacillus pleuropneumoniae transferrin receptor genes  

Microsoft Academic Search

The tbpA and *pi? genes encoding the transferrin receptor proteins Tbpl and Tbp2 from a serotype 7 strain of Actinobacillus pleuropneumoniae were cloned, sequenced, and expressed in Escherichia coli. The tbpB gene was preceded by putative promoter and regulatory sequences and was separated from the downstream tbpA gene by a 13 bp intercistronic sequence suggesting that the two genes may

Guido C. Gonzalez; R.-h. Yu; Paul R. Rosteck; A. B. Schryvers

1995-01-01

295

Multimodality Imaging of Gene Transfer with a Receptor-Based Reporter Gene  

PubMed Central

Gene therapy trials have traditionally used tumor and tissue biopsies for assessing the efficacy of gene transfer. Non-invasive imaging techniques offer a distinct advantage over tissue biopsies in that the magnitude and duration of gene transfer can be monitored repeatedly. Human somatostatin receptor subtype 2 (SSTR2) has been used for the nuclear imaging of gene transfer. To extend this concept, we have developed a somatostatin receptor–enhanced green fluorescent protein fusion construct (SSTR2-EGFP) for nuclear and fluorescent multimodality imaging. Methods An adenovirus containing SSTR2-EGFP (AdSSTR2-EGFP) was constructed and evaluated in vitro and in vivo. SCC-9 human squamous cell carcinoma cells were infected with AdEGFP, AdSSTR2, or AdSSTR2-EGFP for in vitro evaluation by saturation binding, internalization, and fluorescence spectroscopy assays. In vivo biodistribution and nano-SPECT imaging studies were conducted with mice bearing SCC-9 tumor xenografts directly injected with AdSSTR2-EGFP or AdSSTR2 to determine the tumor localization of 111In-diethylenetriaminepentaacetic acid (DTPA)-Tyr3-octreotate. Fluorescence imaging was conducted in vivo with mice receiving intratumoral injections of AdSSTR2, AdSSTR2-EGFP, or AdEGFP as well as ex vivo with tissues extracted from mice. Results The similarity between AdSSTR2-EGFP and wild-type AdSSTR2 was demonstrated in vitro by the saturation binding and internalization assays, and the fluorescence emission spectra of cells infected with AdSSTR2-EGFP was almost identical to the spectra of cells infected with wild-type AdEGFP. Biodistribution studies demonstrated that the tumor uptake of 111In-DTPA-Tyr3-octreotate was not significantly different (P > 0.05) when tumors (n = 5) were injected with AdSSTR2 or AdSSTR2-EGFP but was significantly greater than the uptake in control tumors. Fluorescence was observed in tumors injected with AdSSTR2-EGFP and AdEGFP in vivo and ex vivo but not in tumors injected with AdSSTR2. Although fluorescence was observed, there were discrepancies between in vivo imaging and ex vivo imaging as well as between nuclear imaging and fluorescent imaging. Conclusion These studies showed that the SSTR2-EGFP fusion construct can be used for in vivo nuclear and optical imaging of gene transfer.

Chen, Ron; Parry, Jesse J.; Akers, Walter J.; Berezin, Mikhail Y.; El Naqa, Issam M.; Achilefu, Samuel; Edwards, W. Barry; Rogers, Buck E.

2010-01-01

296

Modulation of adipogenesis-related gene expression by estrogen-related receptor ? during adipocytic differentiation  

Microsoft Academic Search

Estrogen-related receptor ? (ERR?) is an orphan nuclear receptor that regulates cellular energy metabolism by modulating gene expression involved in oxidative metabolism and mitochondrial biogenesis in brown adipose tissue and heart. However, the physiological role of ERR? in adipogenesis and the development of white adipose tissue has not been well studied. Here we show that ERR? was up-regulated in murine

Mayumi Kubo; Nobuhiro Ijichi; Kazuhiro Ikeda; Kuniko Horie-Inoue; Satoru Takeda; Satoshi Inoue

2009-01-01

297

Leptin Receptor Gene Polymorphisms Are Associated with Insulin in Obese Women with Impaired Glucose Tolerance  

Microsoft Academic Search

Leptin receptors are present on b-cells as well as on muscle and fat cells, thus enabling leptin to modulate both insulin secretion and insulin action. Leptin inhibits especially the glucose-stimulated in- sulin secretion from pancreatic cells. The leptin receptor (LEPR) gene could thus play a role in the regulation of glucose and insulin after an oral glucose load. Therefore, the

M. WAUTERS; I. MERTENS; T. RANKINEN; M. CHAGNON; C. BOUCHARD; L. VAN GAAL

2010-01-01

298

CHARACTERIZATION OF AN S-LOCUS RECEPTOR PROTEIN KINASE-LIKE GENE FROM PEACH  

Technology Transfer Automated Retrieval System (TEKTRAN)

A receptor-like protein kinase (Ppsrkl1) was isolated from a peach bark cDNA library prepared with RNAs isolated from bark collected in December (cold acclimated). Sequence analysis indicates that this gene is related to the S-locus family of receptor protein kinases (SRKs) and that it shares great...

299

Role for rearranged variable gene segments in directing secondary T cell receptor recombination  

Microsoft Academic Search

During the recombination of variable (V) and joining (J) gene segments at the T cell receptor ? locus, a V?J? joint resulting from primary rearrangement can be replaced by subsequent rounds of secondary rearrangement that use progressively more 5? V? segments and progressively more 3? J? segments. To understand the mechanisms that target secondary T cell receptor ? recombination, we

Abbas Hawwari; M. S. Krangel

2007-01-01

300

A hypervariable segment in the human dopamine receptor D 4 ( DRD4 ) gene  

Microsoft Academic Search

The human dopamine D4 receptor contains a novel polymorphism within the putative third cytoplasmic loop of the protein. The polymorphism is characterized by a varying number of direct imperfect 48-bp repeats in the gene. Pharmacological characterization has suggested that this receptor is the site through which the atypical neuroleptic clozapine exerts its antipsychotic action and that some polymorphic variants display

Jay B. Lichter; Cathy L. Barr; James L. Kennedy; Hubert H. M. Van Tol; Kenneth K. Kidd; Kenneth J. Livak

1993-01-01

301

Association Between A2a Receptor Gene Polymorphisms and Caffeine-Induced Anxiety  

Microsoft Academic Search

The adenosine receptor system, which mediates the psychoactive effects of caffeine, is also thought to be involved in the regulation of anxiety. In this study, we examined the association between variations in anxiogenic responses to caffeine and polymorphisms in the A1 and A2a adenosine receptor genes. Healthy, infrequent caffeine users (N=94) recorded their subjective mood states following a 150 mg

Karen Alsene; Jürgen Deckert; Philipp Sand; Harriet de Wit

2003-01-01

302

Identification of deletions in the human low density lipoprotein receptor gene  

Microsoft Academic Search

DNA samples from 70 unrelated UK patients with heterozygous familial hypercholesterolaemia were screened by Southern blot hybridisation with a 5' fragment of the human low density lipoprotein (LDL) receptor cDNA. In the majority of cases, the restriction fragment pattern of the LDL receptor gene was indistinguishable from that observed in normal subjects. However, three patients were found to have a

B Horsthemke; A Dunning; S Humphries

1987-01-01

303

The c-erb-A gene encodes a thyroid hormone receptor  

Microsoft Academic Search

The cDNA sequence of human c-erb-A, the cellular counterpart of the viral oncogene v-erb-A, indicates that the protein encoded by the gene is related to the steroid hormone receptors. Binding studies with the protein show it to be a receptor for thyroid hormones.

Cary Weinberger; Catherine C. Thompson; Estelita S. Ong; Roger Lebo; Donald J. Gruol; Ronald M. Evans

1986-01-01

304

Analysis of the human folate receptor ? gene for an association with neural tube defects  

Microsoft Academic Search

The folate receptor ? (FR?) gene encodes a receptor that binds and transports 5-methyltetrahydrofolate. FR? polymorphisms may potentially alter folate delivery and are likely candidates for an association with neural tube defect (NTD) risk. To look for association between FR? polymorphisms we studied NTD-affected children and their parents (254 triads) recruited throughout Ireland and a control population of 296 pregnant

Valerie B O’Leary; James L Mills; Peadar N Kirke; Anne Parle-McDermott; Deborah A Swanson; Andrea Weiler; Faith Pangilinan; Mary Conley; Anne M Molloy; Miriam Lynch; Christopher Cox; John M Scott; Lawrence C Brody

2003-01-01

305

Association study between the dopamine D4 receptor gene and schizophrenia  

Microsoft Academic Search

The dopamine D4 receptor is of major interest in schizophrenia research due to its high affinity for the atypical neuroleptic clozapine and a high degree of variability in the receptor gene (DRD4). Although several genetic linkage analyses performed on schizophrenia multiplex families from different regions of the world have either excluded or failed to prove that DRD4 is a major

Arturas Petronis; Fabio Macciardi; Andrew Athanassiades; Andrew D. Paterson; Massimiliano Verga; Herbert Y. Meltzer; Philip Cola; Janet A. Buchanan; Hubert H. M. Van Tol; James L. Kennedy

1995-01-01

306

Evolution of the sweet taste receptor gene Tas1r2 in bats  

Microsoft Academic Search

Taste perception is an important component of an animal's fitness. The identification of vertebrate taste receptor genes in the last decade has enabled molecular genetic studies of the evolution of taste perception in the context of the ecology and dietary preferences of organisms. Although such analyses have been conducted in a number of species for bitter taste receptors, a similar

Huabin Zhao; Yingying Zhou; C. Miguel Pinto; Pierre Charles-Dominique; Jorge Galindo-Gonzalez; Shuyi Zhang; Jianzhi Zhang

2010-01-01

307

Agrin Can Mediate Acetylcholine Receptor Gene Expression in Muscle by Aggregation of Muscle-derived Neuregulins  

Microsoft Academic Search

The neural isoforms of agrin can stimulate transcription of the acetylcholine receptor (AChR) e subunit gene in electrically active muscle fibers, as does the motor neuron upon the formation of a neuromuscu- lar junction. It is not clear, however, whether this induc- tion involves neuregulins (NRGs), which stimulate AChR subunit gene transcription in vitro by activating ErbB receptors. In this

Thomas Meier; Fabrizio Masciulli; Chris Moore; Fabrice Schoumacher; Urs Eppenberger; Alain J. Denzer; Graham Jones; Hans Rudolf Brenner

1998-01-01

308

Gastrin receptor genes are expressed in gastric parietal and enterochromaffin-like cells of Mastomys natalensis  

Microsoft Academic Search

Although gastric enterochromaffin-like (ECL) carcinoid tumors are known to develop in patients with long-standing hypergastrinemia, the expression of the gastrin receptor gene in ECL cells has not yet been demonstrated. Therefore, this study was designed to examine gastrin receptor gene expression in ECL cells.Mastomys gastric mucosal cells isolated by enzyme dispersion were separated into 10 fractions (F1–10) by centrifugal elutriation.

Masakyo Asahara; Yoshikazu Kinoshita; Hirohisa Nakata; Yumi Matsushima; Yoko Naribayashi; Akira Nakamura; Toshimitsu Matsui; Kazuo Chihara; Jun Yamamoto; Atsushi Ichikawa; Tsutomu Chiba

1994-01-01

309

Diversity of killer cell immunoglobulin-like receptor genes in Southern Turkey  

Microsoft Academic Search

Killer cell immunoglobulin-like receptors (KIRs) are a family of inhibitory and activating receptors expressed by natural\\u000a killer (NK) cells and regulate NK cells’ activity. KIR genes are highly polymorphic markers, characterized by a wide diversity,\\u000a and can therefore be considered as good population genetic markers. The aim of this study was to determine KIR gene frequencies,\\u000a ratios of haplotypes and

Ozlem Goruroglu Ozturk; Gurbuz Polat; Ugur Atik

310

Reappraisal of the serotonin 5HT 1B receptor gene in alcoholism: of mice and men  

Microsoft Academic Search

Because pharmacological and genetic data supported the idea that serotonin receptors of the 5-HT1B type can play a modulatory role in alcohol consumption in both human and rodents, the 5-HT1B receptor gene is considered as a candidate gene for alcohol dependence. However, contradictory results have been reported as a positive association between alcohol dependence, and either the 861C or the

Philip Gorwood; Franck Aissi; Philippe Batel; Jean Adès; Charles Cohen-Salmon; Michel Hamon; Claudette Boni; Laurence Lanfumey

2002-01-01

311

The N-terminal region of the chicken progesterone receptor specifies target gene activation  

Microsoft Academic Search

Steroid hormone recepTo Whom It May Concern:rs belong to a family of nuclear receptors that trigger transcriptional activation of target genes by specific binding to DNA recognition sequences, usually located in the 5'-flanking region of the target gene. Nuclear receptors appear to be segmented proteins1 and extensive structure-function analyses have attempted to elucidate the functional significance of individual segments. Two

Laszlo Tora; Hinrich Gronemeyer; Bernard Turcotte; Marie-Pierre Gaub; Pierre Chambon

1988-01-01

312

Sensory experience and sensory activity regulate chemosensory receptor gene expression in Caenorhabditis elegans  

Microsoft Academic Search

Changes in the environment cause both short-term and long-term changes in an animal's behavior. Here we show that specific sensory experiences cause changes in chemosensory receptor gene expression that may alter sensory perception in the nematode Caenorhabditis elegans. Three predicted chemosensory receptor genes expressed in the ASI chemosensory neurons, srd-1, str-2, and str-3, are repressed by exposure to the dauer

Erin L. Peckol; Emily R. Troemel; Cornelia I. Bargmann

2001-01-01

313

Involvement of a polymorphism in the 5HT2A receptor gene in impulsive behavior  

Microsoft Academic Search

Rationale and objective  Impulsive behavior has been suggested to occur due to a dysfunction of serotonergic 5-HT neurotransmission. After evaluation by a self-reporting measure, a polymorphism in the promoter of the 5-HT2A receptor gene has been proposed to underlie the impulsive behavior; however, this hypothesis is not convincing. In this study, we examined whether this 5-HT2A receptor gene polymorphism is involved

Michio Nomura; Ichiro Kusumi; Masayuki Kaneko; Takuya Masui; Makoto Daiguji; Takeji Ueno; Tsukasa Koyama; Yasuyuki Nomura

2006-01-01

314

The CLAVATA1 Receptor-like Kinase Requires CLAVATA3 for Its Assembly into a Signaling Complex That Includes KAPP and a Rho-Related Protein  

Microsoft Academic Search

The CLAVATA1 ( CLV1 ) and CLAVATA3 ( CLV3 ) genes are required to maintain the balance between cell proliferation and organ formation at the Arabidopsis shoot and flower meristems. CLV1 encodes a receptor-like protein kinase. We have found that CLV1 is present in two protein complexes in vivo. One is z 185 kD, and the other is z 450

Amy E. Trotochaud; Guang Wu; Zhenbiao Yang; Steven E. Clark

1999-01-01

315

Association analysis of peroxisome proliferator-activated receptors gamma gene polymorphisms with asprin hypersensitivity in asthmatics  

PubMed Central

Purpose Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors activated by ligands of the nuclear hormone receptor superfamily. The activation of PPAR? regulates inflammation by downregulating the production of Th2 type cytokines and eosinophil function. In addition, a range of natural substances, including arachidonate pathway metabolites such as 15-hydroxyeicosatetranoic acid (15-HETE), strongly promote PPARG expression. Therefore, genetic variants of the PPARG gene may be associated with the development of aspirin-intolerant asthma (AIA). We investigated the relationship between single nucleotide polymorphism (SNP) of the PPARG gene and AIA. Methods Based on the results of an oral aspirin challenge, asthmatics (n=403) were categorized into two groups: those with a decrease in FEV1 of 15% or greater (AIA) or less than 15% (aspirin-tolerant asthma, ATA). We genotyped two single nucleotide polymorphisms in the PPARG gene from Korean asthmatics and normal controls (n=449): +34C>G (Pro12Ala) and +82466C>T (His449His). Results Logistic regression analysis showed that +82466C>T and haplotype 1 (CC) were associated with the development of aspirin hypersensitivity in asthmatics (P=0.04). The frequency of the rare allele of +82466C>T was significantly higher in AIA patients than in ATA patients in the recessive model [P=0.04, OR=3.97 (1.08-14.53)]. In addition, the frequency of PPARG haplotype 1 was significantly lower in AIA patients than in ATA patients in the dominant model (OR=0.25, P=0.04). Conclusions The +82466C>T polymorphism and haplotype 1 of the PPARG gene may be linked to increased risk for aspirin hypersensitivity in asthma.

Oh, Sun-Hee; Park, Se-Min; Park, Jong-Sook; Jang, An-Soo; Lee, Yong-Mok; Uh, Soo-Taek; Kim, Young Hoon; Choi, In-Seon; Kim, Mi-Kyeong; Park, Byeong Lae

2009-01-01

316

Detection of Clonal T-Cell Receptor ? Gene Rearrangements in Early Mycosis Fungoides\\/Sezary Syndrome by Polymerase Chain Reaction and Denaturing Gradient Gel Electrophoresis (PCR\\/DGGE)  

Microsoft Academic Search

We used a gene amplification strategy to analyze T-cell receptor (TCR) gene rearrangements in 185 specimens, including mycosis fungoides\\/Sezary syndrome (MF\\/SS), other cutaneous neoplasms, inflammatory dermatoses, reactive lymphoid tissues,and normal skin. Genomic DNA was extracted from lesional tissues and rearrangements of the TCR-? chain gene were amplified using the polymerase chain reaction (PCR) with primers specific for rearrangements involving V?1-8

Gary S. Wood; Rosnn M. Tung; Andreas C. Heaffner; Carol F. Crooks; Shaoyi Liao; Rachaci Orozco; Hendrik Veelken; Marshall E. Kadin; Howard Koh; Peter Heald; Raymond L. Barnhill; Jeffrey Sklar

1994-01-01

317

The evolution of vertebrate somatostatin receptors and their gene regions involves extensive chromosomal rearrangements  

PubMed Central

Background Somatostatin and its related neuroendocrine peptides have a wide variety of physiological functions that are mediated by five somatostatin receptors with gene names SSTR1-5 in mammals. To resolve their evolution in vertebrates we have investigated the SSTR genes and a large number of adjacent gene families by phylogeny and conserved synteny analyses in a broad range of vertebrate species. Results We find that the SSTRs form two families that belong to distinct paralogons. We observe not only chromosomal similarities reflecting the paralogy relationships between the SSTR-bearing chromosome regions, but also extensive rearrangements between these regions in teleost fish genomes, including fusions and translocations followed by reshuffling through intrachromosomal rearrangements. These events obscure the paralogy relationships but are still tractable thanks to the many genomes now available. We have identified a previously unrecognized SSTR subtype, SSTR6, previously misidentified as either SSTR1 or SSTR4. Conclusions Two ancestral SSTR-bearing chromosome regions were duplicated in the two basal vertebrate tetraploidizations (2R). One of these ancestral SSTR genes generated SSTR2, -3 and -5, the other gave rise to SSTR1, -4 and -6. Subsequently SSTR6 was lost in tetrapods and SSTR4 in teleosts. Our study shows that extensive chromosomal rearrangements have taken place between related chromosome regions in teleosts, but that these events can be resolved by investigating several distantly related species.

2012-01-01

318

The aryl hydrocarbon receptor repressor is a putative tumor suppressor gene in multiple human cancers  

PubMed Central

The aryl hydrocarbon receptor repressor (AHRR) is a bHLH/Per-ARNT-Sim transcription factor located in a region of chromosome 5 (5p15.3) that has been proposed to contain one or more tumor suppressor genes. We report here consistent downregulation of AHRR mRNA in human malignant tissue from different anatomical origins, including colon, breast, lung, stomach, cervix, and ovary, and demonstrate DNA hypermethylation as the regulatory mechanism of AHRR gene silencing. Knockdown of AHRR gene expression in a human lung cancer cell line using siRNA significantly enhanced in vitro anchorage-dependent and -independent cell growth as well as cell growth after transplantation into immunocompromised mice. In addition, knockdown of AHRR in non-clonable normal human mammary epithelial cells enabled them to grow in an anchorage-independent manner. Further, downregulation of AHRR expression in the human lung cancer cell line conferred resistance to apoptotic signals and enhanced motility and invasion in vitro and angiogenic potential in vivo. Ectopic expression of AHRR in tumor cells resulted in diminished anchorage-dependent and -independent cell growth and reduced angiogenic potential. These results therefore demonstrate that AHRR is a putative new tumor suppressor gene in multiple types of human cancers.

Zudaire, Enrique; Cuesta, Natalia; Murty, Vundavalli; Woodson, Karen; Adams, Lisa; Gonzalez, Nieves; Martinez, Alfredo; Narayan, Gopeshwar; Kirsch, Ilan; Franklin, Wilbur; Hirsch, Fred; Birrer, Michael; Cuttitta, Frank

2008-01-01

319

Resequencing of the auxiliary GABA(B) receptor subunit gene KCTD12 in chronic tinnitus.  

PubMed

Tinnitus is a common and often incapacitating hearing disorder marked by the perception of phantom sounds. Susceptibility factors remain largely unknown but GABA(B) receptor signaling has long been implicated in the response to treatment and, putatively, in the etiology of the disorder. We hypothesized that variation in KCTD12, the gene encoding an auxiliary subunit of GABA(B) receptors, could help to predict the risk of developing tinnitus. Ninety-five Caucasian outpatients with a diagnosis of chronic tinnitus were systematically screened for mutations in the KCTD12 open reading frame and the adjacent 3' untranslated region by Sanger sequencing. Allele frequencies were determined for 14 known variants of which three (rs73237446, rs34544607, and rs41287030) were polymorphic. When allele frequencies were compared to data from a large reference population of European ancestry, rs34544607 was associated with tinnitus (p = 0.04). However, KCTD12 genotype did not predict tinnitus severity (p = 0.52) and the association with rs34544607 was weakened after screening 50 additional cases (p = 0.07). Pending replication in a larger cohort, KCTD12 may act as a risk modifier in chronic tinnitus. Issues that are yet to be addressed include the effects of neighboring variants, e.g., in the KCTD12 gene regulatory region, plus interactions with variants of GABA(B1) and GABA(B2). PMID:22654739

Sand, P G; Langguth, B; Itzhacki, J; Bauer, A; Geis, S; Cárdenas-Conejo, Z E; Pimentel, V; Kleinjung, T

2012-05-25

320

Resequencing of the auxiliary GABAB receptor subunit gene KCTD12 in chronic tinnitus  

PubMed Central

Tinnitus is a common and often incapacitating hearing disorder marked by the perception of phantom sounds. Susceptibility factors remain largely unknown but GABAB receptor signaling has long been implicated in the response to treatment and, putatively, in the etiology of the disorder. We hypothesized that variation in KCTD12, the gene encoding an auxiliary subunit of GABAB receptors, could help to predict the risk of developing tinnitus. Ninety-five Caucasian outpatients with a diagnosis of chronic tinnitus were systematically screened for mutations in the KCTD12 open reading frame and the adjacent 3? untranslated region by Sanger sequencing. Allele frequencies were determined for 14 known variants of which three (rs73237446, rs34544607, and rs41287030) were polymorphic. When allele frequencies were compared to data from a large reference population of European ancestry, rs34544607 was associated with tinnitus (p = 0.04). However, KCTD12 genotype did not predict tinnitus severity (p = 0.52) and the association with rs34544607 was weakened after screening 50 additional cases (p = 0.07). Pending replication in a larger cohort, KCTD12 may act as a risk modifier in chronic tinnitus. Issues that are yet to be addressed include the effects of neighboring variants, e.g., in the KCTD12 gene regulatory region, plus interactions with variants of GABAB1 and GABAB2.

Sand, P. G.; Langguth, B.; Itzhacki, J.; Bauer, A.; Geis, S.; Cardenas-Conejo, Z. E.; Pimentel, V.; Kleinjung, T.

2012-01-01

321

CCAAT/Enhancer Binding Proteins ? and ? Regulate the Tumor Necrosis Factor Receptor 1 Gene Promoter  

PubMed Central

CCAAT/enhancer binding protein (C/EBP) transcription factors play essential roles in regulating an array of cellular processes, including differentiation, energy metabolism, and inflammation. In this report we demonstrate that both C/EBP? and C/EBP? activate the promoter driving transcription of the tumor necrosis factor receptor 1 (TNFR1). TNFR1 is the major receptor for tumor necrosis factor (TNF), a critical cytokine mediator of the inflammatory response. Although the TNFR1 protein has been shown to be regulated through post-translational modifications, very little is known about the transcriptional regulation of the TNFR1 gene. Here we have identified a specific C/EBP binding site within the TNFR1 promoter, and shown that this site is required for both C/EBP? and C/EBP? activation of the promoter in reporter gene assays. Furthermore, we show that both C/EBP? and C/EBP? are bound to the TNFR1 promoter in cells using chromatin immunoprecipitation assays. Finally, we demonstrate that reducing the level of C/EBP? and C/EBP? expression in cells using siRNA technology leads to decreased expression of the TNFR1 protein. These results suggest that the C/EBP? and C/EBP? transcription factors enhance expression of the TNFR1 protein in cells. Given that TNF and C/EBP? are known to activate each other's expression, C/EBP? may greatly amplify the initial TNF signal through a positive auto-regulatory mechanism.

Bristol, Jillian A.; Morrison, Thomas E.; Kenney, Shannon C.

2009-01-01

322

Cloning of human genes encoding novel G protein-coupled receptors  

SciTech Connect

We report the isolation and characterization of several novel human genes encoding G protein-coupled receptors. Each of the receptors contained the familiar seven transmembrane topography and most closely resembled peptide binding receptors. Gene GPR1 encoded a receptor protein that is intronless in the coding region and that shared identity (43% in the transmembrane regions) with the opioid receptors. Northern blot analysis revealed that GPR1 transcripts were expressed in the human hippocampus, and the gene was localized to chromosome 15q21.6. Gene GPR2 encoded a protein that most closely resembled an interleukin-8 receptor (51% in the transmembrane regions), and this gene, not expressed in the six brain regions examined, was localized to chromosome 17q2.1-q21.3. A third gene, GPR3, showed identity (56% in the transmembrane regions) with a previously characterized cDNA clone from rat and was localized to chromosome 1p35-p36.1. 31 refs., 5 figs., 1 tab.

Marchese, A.; Docherty, J.M.; Heiber, M. [Univ. of Toronto, (Canada)] [and others

1994-10-01

323

Transcriptional Regulation of Mouse   Opioid Receptor Gene: Sp3 Isoforms (M1, M2) Function as Repressors in Neuronal Cells to Regulate the   Opioid Receptor Gene  

Microsoft Academic Search

The 5-flanking region of the mouse opioid receptor (MOR) gene has two promoters, referred to as distal and proximal. MOR mRNA is predominantly initiated by the proximal pro- moter. Previously, several important cis-elements and trans- factors have been shown to play a functional role in the prox- imal promoter of the MOR gene. In this study, we defined another functional,

Hack Sun Choi; Cheol Kyu Hwang; Chun Sung Kim; Kyu Young Song; Ping-Yee Law; Li-Na Wei; Horace H. Loh

2005-01-01

324

Structure and chromosomal localization of the human antidiuretic hormone receptor gene  

SciTech Connect

Applying a genomic DNA-expression approach, the authors cloned the gene and cDNA coding for the human antidiuretic hormone receptor, also called vasopressin V2 receptor' (V2R). The nucleotide sequence of both cloned DNAs provided the information to elucidate the structure of the isolated transcriptional unit. The structure of this gene is unusual in that it is the first G protein-coupled receptor gene that contains two very small intervening sequences, the second of which separates the region encoding the seventh transmembrane region from the rest of the open reading frame. The sequence information was used to synthesize appropriate oligonucleotides to be used as primers in the PCR. The V2R gene was localized by PCR using DNA from hybrid cells as template. The gene was found to reside in the q28-qter portion of the human X chromosome, a region identified as the locus for congential nephrogenic diabetes insipidus. 27 refs., 4 figs.

Seibold, A.; Brabet, P.; Rosenthal, W.; Birnbaumer, M. (Baylor College of Medicine, Houston, TX (United States))

1992-11-01

325

Leptin G-2548A and leptin receptor Q223R gene polymorphisms are not associated with obesity in Romanian subjects  

Microsoft Academic Search

We aimed to investigate whether polymorphisms LEP G-2548A and LEPR Q223R in the human leptin (LEP), and leptin receptor (LEPR) genes are associated with obesity and metabolic traits in a sample of Romanian population. Two hundred and two subjects divided in obese (body mass index, BMI?30kg\\/m2), and non-obese were included in this study. The polymorphisms were genotyped using polymerase chain

Alina Constantin; Gabriela Costache; Anca V. Sima; Cristiana S. Glavce; Maria Vladica; Doina L. Popov

2010-01-01

326

Genome-Wide Analysis of Glucocorticoid Receptor Binding Regions in Adipocytes Reveal Gene Network Involved in Triglyceride Homeostasis  

Microsoft Academic Search

Glucocorticoids play important roles in the regulation of distinct aspects of adipocyte biology. Excess glucocorticoids in adipocytes are associated with metabolic disorders, including central obesity, insulin resistance and dyslipidemia. To understand the mechanisms underlying the glucocorticoid action in adipocytes, we used chromatin immunoprecipitation sequencing to isolate genome-wide glucocorticoid receptor (GR) binding regions (GBRs) in 3T3-L1 adipocytes. Furthermore, gene expression analyses

Chi-Yi Yu; Oleg Mayba; Joyce V. Lee; Joanna Tran; Charlie Harris; Terence P. Speed; Jen-Chywan Wang; Michael J. Pazin

2010-01-01

327

Association of the TGF-? receptor genes with abdominal aortic aneurysm  

PubMed Central

Abdominal aortic aneurysm (AAA) is a multifactorial condition. The transforming growth factor ? (TGF-?) pathway regulates vascular remodeling and mutations in its receptor genes, TGFBR1 and TGFBR2, cause syndromes with thoracic aortic aneurysm (TAA). The TGF-? pathway may be involved in aneurysm development in general. We performed an association study by analyzing all the common genetic variants in TGFBR1 and TGFBR2 using tag single nucleotide polymorphisms (SNPs) in a Dutch AAA case–control population in a two-stage genotyping approach. In stage 1, analyzing 376 cases and 648 controls, three of the four TGFBR1 SNPs and nine of the 28 TGFBR2 SNPs had a P<0.07. Genotyping of these SNPs in an independent cohort of 360 cases and 376 controls in stage 2 confirmed association (P<0.05) for the same allele of one SNP in TGFBR1 and two SNPs in TGFBR2. Joint analysis of the 736 cases and 1024 controls showed statistically significant associations of these SNPs, which sustained after proper correction for multiple testing (TGFBR1 rs1626340 OR 1.32 95% CI 1.11–1.56 P=0.001 and TGFBR2 rs1036095 OR 1.32 95% CI 1.12–1.54 P=0.001 and rs4522809 OR 1.28 95% CI 1.12–1.46 P=0.0004). We conclude that genetic variations in TGFBR1 and TGFBR2 associate with AAA in the Dutch population. This suggests that AAA may develop partly by similar defects as TAA, which in the future may provide novel therapeutic options.

Baas, A F; Medic, J; van 't Slot, R; de Kovel, C G; Zhernakova, A; Geelkerken, R H; Kranendonk, S E; van Sterkenburg, S M; Grobbee, D E; Boll, A P; Wijmenga, C; Blankensteijn, J D; Ruigrok, Y M

2010-01-01

328

Mutations in the promoter region of the androgen receptor gene are not common in males with idiopathic infertility  

Microsoft Academic Search

Molecular studies on the role of the androgen receptor in male infertility have thus far concentrated solely on exonic regions of the androgen receptor gene. We have therefore screened for the first time the androgen receptor gene 59 untranslated region (nucleotides -153 to F237 ) in 240 males with idiopathic infertility for lesions which could potentially impair spermatogenesis. This region

F. J. Ghadessy; S. L. Liow; E. L. Yong

1999-01-01

329

Cocaine-Induced Intracellular Signaling and Gene Expression Are Oppositely Regulated by the Dopamine D1 and D3 Receptors  

Microsoft Academic Search

Repeated exposure to cocaine can induce neuroadaptations in the brain. One mechanism by which persistent changes occur involves alterations in gene expression mediated by the dopamine receptors. Both the dopamine D1 and D3 receptors have been shown to mediate gene expression changes. Moreover, the D1 and D3 receptors are also coexpressed in the same neurons, particularly in the nucleus accumbens

Lu Zhang; Danwen Lou; Hongyuan Jiao; Dongsheng Zhang; Xinkang Wang; Ying Xia; Jianhua Zhang; Ming Xu

2004-01-01

330

No substantial changes in estrogen receptor and estrogen-related receptor orthologue gene transcription in Marisa cornuarietis exposed to estrogenic chemicals???  

PubMed Central

Estrogen receptor orthologues in molluscs may be targets for endocrine disruptors, although mechanistic evidence is lacking. Molluscs are reported to be highly susceptible to effects caused by very low concentrations of environmental estrogens which, if substantiated, would have a major impact on the risk assessment of many chemicals. The present paper describes the most thorough evaluation to-date of the susceptibility of Marisa cornuarietis ER and ERR gene transcription to modulation by vertebrate estrogens in vivo and in vitro. We investigated the effects of estradiol-17? and 4-tert-Octylphenol exposure on in vivo estrogen receptor (ER) and estrogen-related receptor (ERR) gene transcription in the reproductive and neural tissues of the gastropod snail M. cornuarietis over a 12-week period. There was no significant effect (p > 0.05) of treatment on gene transcription levels between exposed and non-exposed snails. Absence of a direct interaction of estradiol-17? and 4-tert-Octylphenol with mollusc ER and ERR protein was also supported by in vitro studies in transfected HEK-293 cells. Additional in vitro studies with a selection of other potential ligands (including methyl-testosterone, 17?-ethinylestradiol, 4-hydroxytamoxifen, diethylstilbestrol, cyproterone acetate and ICI182780) showed no interaction when tested using this assay. In repeated in vitro tests, however, genistein (with mcER-like) and bisphenol-A (with mcERR) increased reporter gene expression at high concentrations only (>10?6 M for Gen and >10?5 M for BPA, respectively). Like vertebrate estrogen receptors, the mollusc ER protein bound to the consensus vertebrate estrogen-response element (ERE). Together, these data provide no substantial evidence that mcER-like and mcERR activation and transcript levels in tissues are modulated by the vertebrate estrogen estradiol-17? or 4-tert-Octylphenol in vivo, or that other ligands of vertebrate ERs and ERRs (with the possible exception of genistein and bisphenol A, respectively) would do otherwise.

Bannister, Richard; Beresford, Nicola; Granger, David W.; Pounds, Nadine A.; Rand-Weaver, Mariann; White, Roger; Jobling, Susan; Routledge, Edwin J.

2013-01-01

331

No substantial changes in estrogen receptor and estrogen-related receptor orthologue gene transcription in Marisa cornuarietis exposed to estrogenic chemicals.  

PubMed

Estrogen receptor orthologues in molluscs may be targets for endocrine disruptors, although mechanistic evidence is lacking. Molluscs are reported to be highly susceptible to effects caused by very low concentrations of environmental estrogens which, if substantiated, would have a major impact on the risk assessment of many chemicals. The present paper describes the most thorough evaluation to-date of the susceptibility of Marisa cornuarietis ER and ERR gene transcription to modulation by vertebrate estrogens in vivo and in vitro. We investigated the effects of estradiol-17? and 4-tert-Octylphenol exposure on in vivo estrogen receptor (ER) and estrogen-related receptor (ERR) gene transcription in the reproductive and neural tissues of the gastropod snail M. cornuarietis over a 12-week period. There was no significant effect (p>0.05) of treatment on gene transcription levels between exposed and non-exposed snails. Absence of a direct interaction of estradiol-17? and 4-tert-Octylphenol with mollusc ER and ERR protein was also supported by in vitro studies in transfected HEK-293 cells. Additional in vitro studies with a selection of other potential ligands (including methyl-testosterone, 17?-ethinylestradiol, 4-hydroxytamoxifen, diethylstilbestrol, cyproterone acetate and ICI182780) showed no interaction when tested using this assay. In repeated in vitro tests, however, genistein (with mcER-like) and bisphenol-A (with mcERR) increased reporter gene expression at high concentrations only (>10(-6)M for Gen and >10(-5)M for BPA, respectively). Like vertebrate estrogen receptors, the mollusc ER protein bound to the consensus vertebrate estrogen-response element (ERE). Together, these data provide no substantial evidence that mcER-like and mcERR activation and transcript levels in tissues are modulated by the vertebrate estrogen estradiol-17? or 4-tert-Octylphenol in vivo, or that other ligands of vertebrate ERs and ERRs (with the possible exception of genistein and bisphenol A, respectively) would do otherwise. PMID:23747549

Bannister, Richard; Beresford, Nicola; Granger, David W; Pounds, Nadine A; Rand-Weaver, Mariann; White, Roger; Jobling, Susan; Routledge, Edwin J

2013-05-17

332

Dopamine Receptor Gene Expression in Human Amygdaloid Nuclei: Elevated D4 Receptor mRNAs in Major Depression  

PubMed Central

Previous findings from this laboratory demonstrating changes in dopamine (DA) transporter and D2 receptors in the amygdaloid complex of subjects with major depression indicate that disruption of dopamine neurotransmission to the amygdala may contribute to behavioral symptoms associated with depression. Quantitative real-time RT-PCR was used to investigate the regional distribution of gene expression of DA receptors in the human amygdala. In addition, relative levels of mRNA of DA receptors in the basal amygdaloid nucleus were measured postmortem in subjects with major depression and normal control subjects. All five subtypes of DA receptor mRNA were detected in all amygdaloid subnuclei, although D1, D2, and D4 receptor mRNAs were more abundant than D3 and D5 mRNAs by an order of magnitude. The highest level of D1 mRNA was found in the central nucleus, whereas D2 mRNA was the most abundant in the basal nucleus. Levels of D4 mRNA were highest in the basal and central nuclei. In the basal nucleus, amounts of D4, but not D1 or D2, mRNAs were significantly higher in subjects with major depression and depressed suicide victims, as compared to control subjects. These findings demonstrate that the D1, D2 and D4 receptors are the major subtypes of DA receptors in the human amygdala. Elevated DA receptor gene expression in depressive subjects further implicates altered dopaminergic transmission in the amygdala in depression.

Xiang, Lianbin; Szebeni, Katalin; Szebeni, Attila; Klimek, Violetta; Stockmeier, Craig A; Karolewicz, Beata; Kalbfleisch, John; Ordway, Gregory A

2008-01-01

333

CAG Repeat Number in the Androgen Receptor Gene and Prostate Cancer.  

PubMed

Prostate cancer (PC) is the second leading cause of cancer deaths in men. The effects of androgens on prostatic tissue are mediated by the androgen receptor (AR) gene. The 5' end of exon 1 of the AR gene includes a polymorphic CAG triplet repeat that numbers between 10 to 36 in the normal population. The length of the CAG repeats is inversely related to the transactivation function of the AR gene. There is controversy over association between short CAG repeat numbers in the AR gene and PC. This retrospective case-control study evaluates the possible effect of short CAG repeats on the AR gene in prostate cancer risk in Macedonian males. A total of 392 male subjects, 134 PC patients, 106 patients with benign prostatic hyperplasia (BPH) and 152 males from the general Macedonian population were enrolled in this study. The CAG repeat length was determined by fluorescent polymerase chain reaction (PCR) amplification of exon1 of the AR gene followed by capillary electrophoresis (CE) on a genetic analyzer. The mean repeat length in PC patients was 21.5 ± 2.65, in controls 22.28 ± 2.86 (p = 0.009) and in BPH patients 22.1 ± 2.52 (p = 0.038). Short CAG repeats (<19) were found in 21.64% of PC patients vs. 9.43% in BPH patients (p = 0.0154). We also found an association of low Gleason score (<7) with short CAG repeat (<19) in PC patients (p = 0.0306), and no association between the age at diagnosis of PC and BPH and CAG repeat length. These results suggest that reduced CAG repeat length may be associated with increased prostate cancer risk in Macedonian men. PMID:24052720

Madjunkova, S; Eftimov, A; Georgiev, V; Petrovski, D; Dimovski, Aj; Plaseska-Karanfilska, D

2012-06-01

334

CAG Repeat Number in the Androgen Receptor Gene and Prostate Cancer  

PubMed Central

Prostate cancer (PC) is the second leading cause of cancer deaths in men. The effects of androgens on prostatic tissue are mediated by the androgen receptor (AR) gene. The 5? end of exon 1 of the AR gene includes a polymorphic CAG triplet repeat that numbers between 10 to 36 in the normal population. The length of the CAG repeats is inversely related to the transactivation function of the AR gene. There is controversy over association between short CAG repeat numbers in the AR gene and PC. This retrospective case-control study evaluates the possible effect of short CAG repeats on the AR gene in prostate cancer risk in Macedonian males. A total of 392 male subjects, 134 PC patients, 106 patients with benign prostatic hyperplasia (BPH) and 152 males from the general Macedonian population were enrolled in this study. The CAG repeat length was determined by fluorescent polymerase chain reaction (PCR) amplification of exon1 of the AR gene followed by capillary electrophoresis (CE) on a genetic analyzer. The mean repeat length in PC patients was 21.5 ± 2.65, in controls 22.28 ± 2.86 (p = 0.009) and in BPH patients 22.1 ± 2.52 (p = 0.038). Short CAG repeats (<19) were found in 21.64% of PC patients vs. 9.43% in BPH patients (p = 0.0154). We also found an association of low Gleason score (<7) with short CAG repeat (<19) in PC patients (p = 0.0306), and no association between the age at diagnosis of PC and BPH and CAG repeat length. These results suggest that reduced CAG repeat length may be associated with increased prostate cancer risk in Macedonian men.

Madjunkova, S; Eftimov, A; Georgiev, V; Petrovski, D; Dimovski, AJ; Plaseska-Karanfilska, D

2012-01-01

335

The nuclear orphan receptors COUP-TF and ARP-1 positively regulate the trout estrogen receptor gene through enhancing autoregulation.  

PubMed Central

The rainbow trout estrogen receptor (rtER) is a positively autoregulated gene in liver cells. In a previous report, we showed that upregulation is mediated by an estrogen response element (ERE) located in the proximal promoter of the gene and that a half binding site for nuclear receptors (5'-TGACCT-3') located 15 bp upstream of the ERE is involved in the magnitude of the estrogen response. We now report that the human orphan receptor COUP-TF and a COUP-TF-like protein from trout liver are able to bind to the consensus half-site. When cotransfected with the rtER gene proximal promoter, COUP-TF had no regulatory functions on its own. Interestingly, COUP-TF enhanced rtER transactivation properties in the presence of estradiol in a dose-dependent manner when cotransfected with the rtER gene promoter. Unliganded retinoid receptor heterodimers had the same helper function as COUP-TF in the presence of estradiol but were switched to repressors when the ligand all-trans-retinoic acid was added. Mutation of the consensus half-site only slightly reduced COUP-TF helper function, suggesting that it actually results from a complex mechanism that probably involves both DNA binding of COUP-TF to the promoter and protein-protein interaction with another transcription factor bound to the promoter. Nevertheless, a DNA-binding-defective mutant of COUP-TF was also defective in ER helper function. Competition footprinting analysis suggested that COUP-TF actually establishes contacts with the consensus upstream half-site and the downstream ERE half-site that would form a DR-24-like response element. Interaction of COUP-TF with the DR-24 element was confirmed in footprinting assays by using nuclear extracts from Saccharomyces cerevisiae expressing COUP-TF. Finally, interaction of COUP-TF with mutants of the rtER gene promoter showed that COUP-TF recognizes the ERE when the upstream half-site is mutated. These data show that COUP-TF may activate transcription through interaction with other nuclear receptors. This cross-talk between liganded nuclear receptors and orphan receptors is likely to modulate the spectrum of action of a particular ligand-receptor complex and may participate in the cell-type specificity of the ligand effect.

Lazennec, G; Kern, L; Valotaire, Y; Salbert, G

1997-01-01

336

Polymorphism in the protease-activated receptor-4 gene region associates with platelet activation and perioperative myocardial injury.  

PubMed

Protease-activated receptors (PAR)-1 and -4 are the principal receptors for thrombin-mediated platelet activation. Functional genetic variation has been described in the human PAR1 gene, but not in the PAR4 gene (F2RL3). We sought to identify variants in and around F2RL3 and to determine their association with perioperative myocardial injury (PMI) after coronary artery bypass graft surgery. We further explored possible mechanisms for F2RL3 single nucleotide polymorphism (SNP) associations with PMI including altered receptor expression and platelet activation. Twenty-three SNPs in the F2RL3 gene region were genotyped in two phases in 934 Caucasian subjects. Platelets from 43 subjects (23 major allele, 20 risk allele) homozygous for rs773857 (SNP with the strongest association with PMI) underwent flow cytometry to assess PAR4 receptor number and response to activation by a specific PAR4 activating peptide (AYPGKF) measured by von Willebrand factor (vWf) binding and P-selectin release and PAC-1 binding. We identified a novel association of SNP rs773857 with PMI (OR = 2.4, P = 0.004). rs773857 risk allele homozygotes have significantly increased platelet counts and platelets showed a significant increase in P-selectin release after activation (P = 0.004). We conclude that rs773857 risk allele homozygotes are associated with risk for increased platelet count and hyperactivity. PMID:22228373

Muehlschlegel, Jochen D; Perry, Tjörvi E; Liu, Kuang-Yu; Fox, Amanda A; Smith, Shane A; Lichtner, Peter; Collard, Charles D; Shernan, Stanton K; Hartwig, John H; Body, Simon C; Hoffmeister, Karin M

2012-01-07

337

Molecular Evolution, Functional Variation, and Proposed Nomenclature of the Gene Family That Includes Sphingomyelinase D in Sicariid Spider Venoms  

PubMed Central

The venom enzyme sphingomyelinase D (SMase D) in the spider family Sicariidae (brown or fiddleback spiders [Loxosceles] and six-eyed sand spiders [Sicarius]) causes dermonecrosis in mammals. SMase D is in a gene family with multiple venom-expressed members that vary in functional specificity. We analyze molecular evolution of this family and variation in SMase D activity among crude venoms using a data set that represents the phylogenetic breadth of Loxosceles and Sicarius. We isolated a total of 190 nonredundant nucleotide sequences encoding 168 nonredundant amino acid sequences of SMase D homologs from 21 species. Bayesian phylogenies support two major clades that we name ? and ?, within which we define seven and three subclades, respectively. Sequences in the ? clade are exclusively from New World Loxosceles and Loxosceles rufescens and include published genes for which expression products have SMase D and dermonecrotic activity. The ? clade includes paralogs from New World Loxosceles that have no, or reduced, SMase D and no dermonecrotic activity and also paralogs from Sicarius and African Loxosceles of unknown activity. Gene duplications are frequent, consistent with a birth-and-death model, and there is evidence of purifying selection with episodic positive directional selection. Despite having venom-expressed SMase D homologs, venoms from New World Sicarius have reduced, or no, detectable SMase D activity, and Loxosceles in the Southern African spinulosa group have low SMase D activity. Sequence conservation mapping shows >98% conservation of proposed catalytic residues of the active site and around a plug motif at the opposite end of the TIM barrel, but ? and ? clades differ in conservation of key residues surrounding the apparent substrate binding pocket. Based on these combined results, we propose an inclusive nomenclature for the gene family, renaming it SicTox, and discuss emerging patterns of functional diversification.

Bodner, Melissa R.; Cordes, Matthew H.J.; Baldwin, Katherine L.; Rynerson, Melody R.; Burns, Scott N.; Zobel-Thropp, Pamela A.

2009-01-01

338

Co-regulation of a large and rapidly evolving repertoire of odorant receptor genes  

PubMed Central

The olfactory system meets niche- and species-specific demands by an accelerated evolution of its odorant receptor repertoires. In this review, we describe evolutionary processes that have shaped olfactory and vomeronasal receptor gene families in vertebrate genomes. We emphasize three important periods in the evolution of the olfactory system evident by comparative genomics: the adaptation to land in amphibian ancestors, the decline of olfaction in primates, and the delineation of putative pheromone receptors concurrent with rodent speciation. The rapid evolution of odorant receptor genes, the sheer size of the repertoire, as well as their wide distribution in the genome, presents a developmental challenge: how are these ever-changing odorant receptor repertoires coordinated within the olfactory system? A central organizing principle in olfaction is the specialization of sensory neurons resulting from each sensory neuron expressing only ~one odorant receptor allele. In this review, we also discuss this mutually exclusive expression of odorant receptor genes. We have considered several models to account for co-regulation of odorant receptor repertoires, as well as discussed a new hypothesis that invokes important epigenetic properties of the system.

Kambere, Marijo B; Lane, Robert P

2007-01-01

339

Polymorphisms within the coding region of the bovine luteinizing hormone receptor gene and their association with fertility traits.  

PubMed

Mutations within a number of genes have been associated with variations in fertility in various mammals. However, to date there have been no such associations reported for cattle. Herein, we describe three single nucleotide polymorphisms (SNPs) in the luteinizing hormone/choriogonadotropin receptor gene of cattle (Bos taurus). These polymorphisms include two missense mutations and one sense mutation, and all are located in areas of conserved synteny. When assessed in terms of haplotypes, these SNPs were significantly associated with variations in cattle fertility and production traits, most notably on calving interval, days to first service and production index (the UK economic index of milk yield measured in poundGB). PMID:17121604

Hastings, N; Donn, S; Derecka, K; Flint, A P; Woolliams, J A

2006-12-01

340

Characterization and mapping of the Rapsn gene encoding the 43-kDa acetylocholine receptor-associated protein  

SciTech Connect

The authors have cloned and characterized mouse genomic DNA containing the gene for the 43-kDa acetylcholine receptor-associated protein. The gene extends over 12 kb and consists of 8 exons. RNase protection and sequence analysis have been used to define the intron/exon boundaries including 174 and 214 bp of 5{prime} and 3{prime} untranslated sequence in exons 1 and 8, respectively. Interestingly, the exon/intron organization is consistent with structural domains predicted from amino acid sequence conservation among 3 species of 43K. Finally, the 43K locus, designated Rapsn, has been mapped to the central region of mouse chromosome 2. 11 refs., 2 figs.

Gautam, M.; Mudd, J.; Copeland, N.G. [Washington Univ. Medical School, St Louis, MO (United States)] [and others

1994-11-15

341

Cloning of the cDNA and gene for a human D sub 2 dopamine receptor  

SciTech Connect

A clone encoding a human D{sub 2} dopamine receptor was isolated from a pituitary cDNA library and sequenced. The deduced protein sequence is 96% identical with that of the cloned rat receptor with one major difference: the human receptor contains an additional 29 amino acids in its putative third cytoplasmic loop. Southern blotting demonstrated the presence of only one human D{sub 2} receptor gene. Two overlapping phage containing the gene were isolated and characterized. DNA sequence analysis of these clones showed that the coding sequence is interrupted by six introns and that the additional amino acids present in the human pituitary receptor are encoded by a single exon of 87 base pairs. The involvement of this sequence in alternative splicing and its biological significance are discussed.

Grady, D.K.; Makam, H.; Stofko, R.E.; Bunzow, J.R.; Civelli, O. (Oregon Health Sciences Univ., Portland (USA)); Marchionni, M.A.; Alfano, M.; Frothingham, L.; Fischer, J.B.; Burke-Howie, K.J.; Server, A.C. (Cambridge NeuroScience Research, Inc., Cambridge, MA (USA))

1989-12-01

342

The second prolactin receptor in Nile tilapia (Oreochromis niloticus): molecular characterization, tissue distribution and gene expression.  

PubMed

Prolactin (PRL) is one of the most versatile hormones found in the pituitary of vertebrates and exerts its actions through binding to a specific PRL receptor (PRLR). Here we describe the cloning and characterization of a second prolactin receptor (ntPRLR2), isolated from the ovary of Nile tilapia (Oreochromis niloticus). The newly identified PRLR cDNA was 2011 bp in length and encoded 529 amino acids. It shared 31.6% identity in nucleotide sequence and 29.2% in deduced amino acid sequence with the first PRLR identified in Nile tilapia (ntPRLR1). Both of these ntPRLRs resemble the long form mammalian PRLRs. The nominated ntPRLR2 was further confirmed as a real prolactin receptor based on its competence to transactivate the beta-casein and c-fos promoters in the transiently ntPRLR2-transfected HEK293 cells. The ntPRLR2 gene also found to encode a 864-bp short form transcript in the ovary, which was confirmed by Northern blot analysis. A tissue distribution study by real-time PCR revealed that the mRNA of both receptors (ntPRLR1 and ntPRLR2) was widely expressed in different tissues, with an extremely high abundance in the osmoregulatory organs, including the gills, intestine and kidney. ntPRLR1 mRNA was more abundant than ntPRLR2 in the testis, while the reverse expression pattern was found in the ovary. In the ovary, ntPRLR2 mRNA demonstrated a distinct gonadal development-dependent expression profile, with significantly higher levels at a sexual mature stage than at sexual recrudescent and sexual regressed stages. When challenged with estradiol, ntPRLR2 mRNA expression was up-regulated by E2, whereas E2 had no significant effect on ntPRLR1. PMID:19757130

Zhang, Yong; Long, Zijie; Li, Yangyuan; Yi, Shibai; Shi, Yu; Ma, Xilan; Huang, Weiren; Lu, Danqi; Zhu, Pei; Liu, Xiaochun; Meng, Zining; Huang, Xigui; Cheng, Christopher H K; Lin, Haoran

2009-09-10

343

The product of a thyroid hormone-responsive gene interacts with thyroid hormone receptors  

PubMed Central

Thyroid hormone is a critical mediator of central nervous system (CNS) development, acting through nuclear receptors to modulate the expression of specific genes. Transcription of the rat hairless (hr) gene is highly up-regulated by thyroid hormone in the developing CNS; we show here that hr is directly induced by thyroid hormone. By identifying proteins that interact with the hr gene product (Hr), we find that Hr interacts directly and specifically with thyroid hormone receptor (TR)—the same protein that regulates its expression. Unlike previously described receptor-interacting factors, Hr associates with TR and not with retinoic acid receptors (RAR, RXR). Hr can act as a transcriptional repressor, suggesting that its interaction with TR is part of a novel autoregulatory mechanism.

Thompson, Catherine C.; Bottcher, Margaret C.

1997-01-01

344

Increased expression of the epidermal growth factor receptor gene in malignant gliomas is invariably associated with gene amplification  

SciTech Connect

Primary malignant gliomas from 63 patients were analyzed to determine the relationship between amplification of the gene encoding the epidermal growth factor receptor (EGFR) and expression of the corresponding mRNA. Twenty-four tumors were found to have amplified the EGFR gene and amplification of other genes occurred in three additional tumors. Hybridization with synthetic RNA probes was used to quantitate mRNA levels in situ. All 24 tumors with amplification of the EGFR gene had high levels of expression of this gene, while none of the 39 tumors without amplification had increased levels. This shows that, in human gliomas, large increases in the expression of the EGFR gene are invariably associated with alterations in gene structure.

Wong, A.J.; Bigner, S.H.; Bigner, D.D.; Kinzler, K.W.; Hamilton, S.R.; Vogelstein, B.

1987-10-01

345

Assignment of the Human Gene for the Low Density Lipoprotein Receptor to Chromosome 19: Synteny of a Receptor, a Ligand, and a Genetic Disease  

Microsoft Academic Search

The availability of a species-specific monoclonal antibody that recognizes the low density lipoprotein (LDL) receptor of human but not hamster origin permitted assignment of the structural gene for the human receptor to chromosome 19. The antibody was used to detect the human LDL receptor in a series of hamster-human somatic cell hybrids by two assays: (i) a structural assay that

Uta Francke; Michael S. Brown; Joseph L. Goldstein

1984-01-01

346

Screening of FSH receptor gene in Argentine women with premature ovarian failure (POF)  

Microsoft Academic Search

Diverse mutations in FSH-receptor (FSHR) gene have been described as possible cause of premature ovarian failure (POF). To investigate the presence of mutations and\\/or polymorphisms in FSHR gene, DNA from 20 POF, 5 of which were diagnosed as resistant ovary syndrome (ROS), and from 44 controls was isolated from peripheral lymphocytes. The complete coding sequence was analysed by PCR followed

Victoria Sundblad; Violeta A Chiauzzi; Maria Eugenia Escobar; Liliana Dain; Eduardo H Charreau

2004-01-01

347

The Estrogen Receptor Locus is Associated with a Major Gene Influencing Litter Size in Pigs  

Microsoft Academic Search

Identification of individual major genes affecting quantitative traits in livestock species has been limited to date. By using a candidate gene approach and a divergent breed cross involving the Chinese Meishan pig, we have shown that a specific allele of the estrogen receptor (ER) locus is associated with increased litter size. Female pigs from synthetic lines with a 50% Meishan

Max Rothschild; Carol Jacobson; David Vaske; Christopher Tuggle; Lizhen Wang; Tom Short; Gregg Eckardt; Shoji Sasaki; Amy Vincent; David McLaren; Olwen Southwood; Hein van der Steen; Alan Mileham; Graham Plastow

1996-01-01

348

Identification of the ancestral killer immunoglobulin-like receptor gene in primates  

Microsoft Academic Search

BACKGROUND: Killer Immunoglobulin-like Receptors (KIR) are essential immuno-surveillance molecules. They are expressed on natural killer and T cells, and interact with human leukocyte antigens. KIR genes are highly polymorphic and contribute vital variability to our immune system. Numerous KIR genes, belonging to five distinct lineages, have been identified in all primates examined thus far and shown to be rapidly evolving.

Jennifer G Sambrook; Arman Bashirova; Hanne Andersen; Mike Piatak; George S Vernikos; Penny Coggill; Jeff D Lifson; Mary Carrington; Stephan Beck

2006-01-01

349

Regulation of the renal angiotensin II receptor gene in acute unilateral ureteral obstruction  

Microsoft Academic Search

Regulation of the renal angiotensin II receptor gene in acute unilateral ureteral obstruction. We have shown that acute (24-hr) unilateral ureteral obstruction (UUO) induces the genes encoding for renin, in juxtaglomerular apparatuses and in tubules, for angiotensin converting enzyme in vascular endothelial cells, and for angiotensinogen in perivascular fat. These molecular changes occur in temporal association to marked reductions in

J Luis Pimentel; Susheng Wang; Manuel Martinez-Maldonado

1994-01-01

350

Embryo brain kinase: a novel gene of the eph\\/elk receptor tyrosine kinase family  

Microsoft Academic Search

A new gene belonging to the Eph\\/Eck\\/Elk receptor tyrosine kinase family has been cloned from mouse brain. The gene maps to mouse chromosome 4. In the adult brain it is expressed exclusively and abundantly in the hippocampus. We propose to name it Ebk (embryo brain kinase), as in situ hybridisation shows expression in many parts of the developing mouse brain.

Jonathan Ellis; Qiurong Liu; Martin Breitman; Nancy A. Jenkins; Debra J. Gilbert; Neal G. Copeland; Heidi V. Tempest; Simon Warren; Elizabeth Muir; Heather Schilling; Fred A. Fletcher; Steven F. Ziegler; John H. Rogers

1995-01-01

351

T Cell Receptor Gene Deletion Circles Identify Recent Thymic Emigrants in the Peripheral T Cell Pool  

Microsoft Academic Search

Progenitor cells undergo T cell receptor (TCR) gene rearrangements during their intrathymic differentiation to become T cells. Rearrangements of the variable (V), diversity (D), and joining (J) segments of the TCR genes result in deletion of the intervening chromosomal DNA and the formation of circular episomes as a byproduct. Detection of these extrachromosomal excision circles in T cells located in

Fan-Kun Kong; Chen-Lo H. Chen; Adrien Six; Richard D. Hockett; Max D. Cooper

1999-01-01

352

Association Studies on Ghrelin and Ghrelin Receptor Gene Polymorphisms With Obesity  

Microsoft Academic Search

Ghrelin exerts a stimulatory effect on appetite and regulates energy homeostasis. Ghrelin gene variants have been shown to be associated with metabolic traits, although there is evidence suggesting linkage and association with obesity and the ghrelin receptor (GHSR). We hypothesized that these genes are good candidates for susceptibility to obesity. Direct sequencing identified 12 ghrelin single-nucleotide polymorphisms (SNPs) and 8

Maria Gueorguiev; Cécile Lecoeur; David Meyre; Michael Benzinou; Charles A. Mein; Anke Hinney; Vincent Vatin; Jacques Weill; Barbara Heude; Johannes Hebebrand; Ashley B. Grossman; Márta Korbonits; Philippe Froguel

2009-01-01

353

The Dopamine D2 Receptor Locus as a Modifying Gene in Neuropsychiatric Disorders  

Microsoft Academic Search

I polymorphism of the dopamine D2 receptor (DRD2) gene has been earlier reported to occur in 69% of alcoholics, compared with 20% of controls. Other research has reported no significant difference in the prevalence of the A1 allele in alcoholics vs controls and no evidence that the DRD2 gene was linked to alcoholism. We hypothesized that these seemingly conflicting results

David E. Comings; Brenda G. Comings; Donn Muhleman; George Dietz; Bejan Shahbahrami; David Tast; Ellen Knell; Pat Kocsis; Rubin Baumgarten; Bruce W. Kovacs; Deborah L. Levy; Melissa Smith; Richard L. Borison; D. Durrell Evans; Daniel N. Klein; James MacMurray; Jeffrey M. Tosk; Jeffrey Sverd; Reinhard Gysin; Steven D. Flanagan

2010-01-01

354

Gene expression profiling reveals novel regulation by bisphenol-A in estrogen receptor- ?-positive human cells  

Microsoft Academic Search

Bisphenol-A (BPA) shows proliferative actions in uterus and mammary glands and may influence the development of male and female reproductive tracts in utero or during early postnatal life. Because of its ability to function as an estrogen receptor (ER) agonist, BPA has the potential to disrupt normal endocrine signaling through regulation of ER target genes. Some genes are regulated by

David W. Singleton; Yuxin Feng; Jun Yang; Alvaro Puga; Adrian V. Lee; Sohaib A.. Khan

2006-01-01

355

Localization of the adenosine A1 receptor subtype gene (ADORA1) to chromosome 1q32.1  

SciTech Connect

Adenosine, acting through its receptors, exerts effects on almost all organ systems, influencing a diversity of physiological responses, including the inhibition of neurotransmitter release, the modulation of cardiac rhythmicity and contractility, and the potentiation of IgE-dependent mediator release. Adenosine receptors belong to the G protein-coupled receptor superfamily, a class of cell-surface receptors that, when activated, couple to a heterotrimeric G protein complex to effect signal transduction. Molecular cloning and subsequent pharmacological and biochemical analyses have led to the identification of four different subtypes of adenosine receptor. The A3 receptor has been localized to chromosome 3 in the mouse by interspecific backcross analysis, suggesting a human chromosomal localization of 1p13 from known mouse-human linkage homologies. We have previously mapped the A2b adenosine receptor subtype to chromosome 17p11.2-p12 using fluorescence in situ hybridization (FISH) and PCR-based screening of somatic cell hybrid DNAs. A previous report has concluded that the Al and A2a receptor subtypes are localized on chromosome 22q11.2-q13.1 and 11q11-q13, respectively, but conflicts with that of MacCollin et al., who have mapped the A2a gene to chromosome 22. In this report, we show that the human A1 adenosine receptor subtype does not map to chromosome 22q11.2-q13.1, but is instead localized on chromosome 1q32. 13 refs., 1 fig.

Townsend-Nicholson, A.; Schofield, P.R. [Garvan Institute for Medical Research, New South Wales (Australia); Baker, E. [Women`s and Children`s Hospital, Adelaide (Australia)] [and others

1995-03-20

356

Age at first sexual intercourse, genes, and social context: evidence from twins and the dopamine D4 receptor gene.  

PubMed

We carried out two distinct types of genetic analysis with data from the National Longitudinal Study of Adolescent Health. The first was a non-DNA twin analysis using monozygotic (identical) and same-sex dizygotic (fraternal) twins. The second analysis investigates the association between age at first sexual intercourse and the 48-bp repeat polymorphism in the dopamine receptor D4 gene (DRD4). The twin analysis shows that MZ twins correlate their timing of first sex to a much greater extent than do the same-sex DZ twins. Our analysis of the polymorphisms in DRD4 indicates that those with an any-3R genotype experienced a risk of first sexual intercourse 23% (p = .016), 233% (p = .0001), 28% (p = .012), and 69% (p = .006) higher than those with an other/other (or any-4R) genotype in the all-ethnicities (n = 2,552), Asian, white, and Hispanic samples, respectively. The risk of first sex does not differ between the two genotypes in the African American sample. These results were obtained after adjusting the standard socioeconomic covariates, including gender, parental education, family structure, and community poverty in the regression model. Evidence from both twin and genetic-variant analyses points to a role of genes in the timing of first sexual intercourse. PMID:17236545

Guo, Guang; Tong, Yuying

2006-11-01

357

Androgen Receptor Repression of GnRH Gene Transcription  

PubMed Central

Alterations in androgen levels lead to reproductive defects in both males and females, including hypogonadotropic hypogonadism, anovulation, and infertility. Androgens have been shown to down-regulate GnRH mRNA levels through an androgen receptor (AR)-dependent mechanism. Here, we investigate how androgen regulates expression from the GnRH regulatory region in the GT1-7 cell line, a model of GnRH neurons. A synthetic androgen, R1881, repressed transcription from the GnRH promoter (GnRH-P) in an AR-dependent manner, and liganded AR associated with the chromatin at the GnRH-P in live GT1-7 cells. The three known octamer-binding transcription factor-1 (Oct-1) binding sites in GnRH-P were required for AR-mediated repression, although other sequences were also involved. Although a multimer of the consensus Oct-1 binding site was not repressed, a multimer of the cluster of Oct-1, Pre-B cell leukemia transcription factor (Pbx)/Prep, and NK2 homeobox 1 (Nkx2.1) binding sites, found at ?106/?91 in GnRH-P, was sufficient for repression. In fact, overexpression of any of these factors disrupted the androgen response, indicating that a balance of factors in this tripartite complex is required for AR repression. AR bound to this region in EMSA, indicating a direct interaction of AR with DNA or with other transcription factors bound to GnRH-P at this sequence. Collectively, our data demonstrate that GnRH transcription is repressed by AR via multiple sequences in GnRH-P, including three Oct-1 binding sites, and that this repression requires the complex interaction of several transcription factors.

Brayman, Melissa J.; Pepa, Patricia A.; Berdy, Sara E.

2012-01-01

358

Ontogeny of mRNA abundance of nuclear receptors and nuclear receptor target genes in young cattle.  

PubMed

After birth the development of appropriate detoxification mechanisms is important. Nuclear receptors (NR), such as constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor-alpha (PPARalpha), retinoid receptors (RAR, RXR), and NR target genes are involved in the detoxification of exogenous and endogenous substances. We quantified abundances of hepatic mRNA of NR and several NR target genes (cytochromes, CYP; cytochrome P450 reductase, CPR; UDP-glucuronosyl transferase, UDP) in calves at different ages. Gene expression was quantified by real-time RT-PCR. Abundance of mRNA of CAR and PXR increased from low levels at birth in pre-term calves (P0) and full-term calves (F0) to higher levels in 5-day-old calves (F5) and in 159-day-old veal calves (F159), whereas mRNA levels of PPARalpha did not exhibit significant ontogenetic changes. RARbeta mRNA levels were higher in F5 and F159 than in F0, whereas no age differences were observed for RARalpha levels. Levels of RXRalpha and RXRbeta mRNA were lower in F5 than in P0 and F0. Abundance of CYP2C8 and CYP3A4 increased from low levels in P0 and F0 to higher levels in F5 and to highest levels in F159. Abundance of CPR was transiently decreased in F0 and F5 calves. Levels of UGT1A1 mRNA increased from low levels in P0 and F0 to maximal level in F5 and F159. In conclusion, mRNA levels of NR and NR target genes exhibited ontogenetic changes that are likely of importance for handling of xeno- and endobiotics with increasing age. PMID:16236479

Greger, D L; Philipona, C; Blum, J W

2005-10-03

359

PET/CT imaging of human somatostatin receptor 2 (hsstr2) as reporter gene for gene therapy  

NASA Astrophysics Data System (ADS)

Localized information on region-selective gene expression in small animals is widely obtained by use of reporter genes inducing light emission. Using these reporter genes for imaging deep inside the human body fluorescent probes are hindered by attenuation, scattering and possible fluorescence quenching. This can be overcome by use of radio-peptide receptors as reporter genes. Therefore, the feasibility of the somatostatin receptor 2 expression vector system for expression imaging was checked against a control vector containing luciferase gene. For in vivo transduction of vector DNA into the rat forelimb muscles the in vivo electroporation technique was chosen because of its high regio-selectivity. The gene expression was imaged by high-sensitive CCD camera (luciferase activity) and by PET/CT using a Ga-68-DOTATOC as radio peptide probe. The relative sstr2 expression was enhanced by gene transduction at maximum to a factor of 15. The PET/CT images could be fully quantified. The above demonstrated feasibility of radio-peptide PET/CT reporter gene imaging may serve in the future as a tool for full quantitative understanding of regional gene expression, especially in large animals and humans.

Hofmann, M.; Gazdhar, A.; Weitzel, T.; Schmid, R.; Krause, T.

2006-12-01

360

Association analysis of retinoic acid receptor beta (RAR?) gene with high myopia in Chinese subjects  

PubMed Central

Purpose High myopia or pathological myopia is a common refractive error. Individuals with high myopia are subject to increased risk of serious eye complications. Accumulating evidence has demonstrated the role for heritability in ocular growth and in the development of high myopia. Retinoic acid and retinoic acid receptors play important roles in ocular development and in experimentally induced myopia. The purpose of this study was to determine if high myopia is associated with single nucleotide polymorphism (SNP) variants in the retinoic acid receptor beta (RAR?) gene in Chinese subjects. Methods DNA samples were purified from venous lymphocytes of 175 unrelated Chinese patients with high myopia (less than ?8.00 diopters) and 101 Chinese control subjects without high myopia (±1.00 diopters). Direct nucleotide sequence analysis in the RAR? gene was performed, and the detected variations were further confirmed by reverse sequencing. Allelic frequencies of all detected SNPs were assessed for Hardy–Weinberg equilibrium. Results Five variations in RAR? were detected in Chinese subjects with high myopia, including 32574G>A, 32629G>A, 32645C>T, 32647T>G, and 151973C>T, of which only 32647T>G (NCBI notes as rs58244688 and rs2067964) had already been reported. The majority of SNP genotypes were heterozygous. While 32647T>G, 32629G>A, and 32645C>T were located in introns and 32574G>A and 151973C>T were located in coding regions, none of the SNPs affected the amino acid sequence. In the present study, no evidence of association was found between variations in the nucleotide sequence of RAR? and high myopia. Conclusions Five SNP variants in RAR? were detected in Chinese subjects with high myopia, none of them were associated significantly with high myopia. Further studies are needed to identify which genes are responsible for high myopia.

Ding, Yang; Chen, Xiaoyan; Yan, Dongsheng; Xue, Anquan; Lu, Fan; Qu, Jia

2010-01-01

361

Precise mapping of the brain [alpha][sub 2]-adrenergic receptor gene within chromosome 4p16  

SciTech Connect

The gene encoding the brain [alpha][sub 2]-adrenergic receptor (ADRA2C) is located on human chromosome 4. It has been circumstantially associated with a number of human disorders, including Parkinson disease, panic disorders, and Huntington disease (HD). Using somatic cell hybrids, the authors localized the gene to chromosome 4p16 distal to P8 (D4S62). To investigate this locus further, they isolated several cosmid clones covering the entire gene. The gene was found to be intronless. Two (GT)[sub n] repeats in close proximity to the ADRAC2 gene were analyzed and used to define its precise location. Linkage disequilibrium studies of one microsatellite in HD families showed strong nonrandom association to the HD mutation, indicating its tight linkage to the HD gene. The investigation of families carrying recombinant chromosomes, pulsed-field analysis, and genomic walking mapped the ADRAC2 gene adjacent to D4S81, 500 kb proximal to the HD gene. The newly defined microsatellites at the ADRAC2 locus, its precise localization within 4p16, and the detailed PCR conditions facilitate the identification of any defect caused by this gene. 22 refs., 4 figs., 2 tabs.

Riess, O.; Siedlaczck, I.; Potisek, S.; Epplen, J.T. (Ruhr Univ., Bochum (Germany)); Thies, U. (Univ. of Goettingen (Germany)); Graham, R.; Theilmann, J.; Hayden, M.R. (Univ. of British Columbia, Vancouver (Canada)); Grimm, T. (Univ. of Wuerzburg (Germany))

1994-01-15

362

Coordinated DNA methylation and gene expression changes in smoker alveolar macrophages: specific effects on VEGF receptor 1 expression  

PubMed Central

Cigarette smoking is implicated in numerous diseases, including emphysema and lung cancer. The clinical expression of lung disease in smokers is not well explained by currently defined variations in gene expression or simple differences in smoking exposure. Alveolar macrophages play a critical role in the inflammation and remodeling of the lung parenchyma in smoking-related lung disease. Significant gene expression changes in alveolar macrophages from smokers have been identified. However, the mechanism for these changes remains unknown. One potential mechanism for smoking-altered gene expression is via changes in cytosine methylation in DNA regions proximal to gene-coding sequences. In this study, alveolar macrophage DNA from heavy smokers and never smokers was isolated and methylation status at 25,000 loci determined. We found differential methylation in genes from immune-system and inflammatory pathways. Analysis of matching gene expression data demonstrated a parallel enrichment for changes in immune-system and inflammatory pathways. A significant number of genes with smoking-altered mRNA expression had inverse changes in methylation status. One gene highlighted by this data was the FLT1, and further studies found particular up-regulation of a splice variant encoding a soluble inhibitory form of the receptor. In conclusion, chronic cigarette smoke exposure altered DNA methylation in specific gene promoter regions in human alveolar macrophages.

Philibert, Robert A.; Sears, Rory A.; Powers, Linda S.; Nash, Emma; Bair, Thomas; Gerke, Alicia K.; Hassan, Ihab; Thomas, Christie P.; Gross, Thomas J.; Monick, Martha M.

2012-01-01

363

A novel human gene encoding a G-protein-coupled receptor (GPR15) is located on chromosome 3.  

PubMed

We used sequence similarities among G-protein-coupled receptor genes to discover a novel receptor gene. Using primers based on conserved regions of the opioid-related receptors, we isolated a PCR product that was used to locate the full-length coding region of a novel human receptor gene, which we have named GPR15. A comparison of the amino acid sequence of the receptor encoded by GPR15 with other receptors revealed that it shared sequence identity with the angiotensin II AT1 and AT2 receptors, the interleukin 8b receptor, and the orphan receptors GPR1 and AGTL1. GPR15 was mapped to human chromosome 3q11.2-q13.1. PMID:8838812

Heiber, M; Marchese, A; Nguyen, T; Heng, H H; George, S R; O'Dowd, B F

1996-03-15

364

Small noncoding differentially methylated copy-number variants, including lncRNA genes, cause a lethal lung developmental disorder  

PubMed Central

An unanticipated and tremendous amount of the noncoding sequence of the human genome is transcribed. Long noncoding RNAs (lncRNAs) constitute a significant fraction of non-protein-coding transcripts; however, their functions remain enigmatic. We demonstrate that deletions of a small noncoding differentially methylated region at 16q24.1, including lncRNA genes, cause a lethal lung developmental disorder, alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), with parent-of-origin effects. We identify overlapping deletions 250 kb upstream of FOXF1 in nine patients with ACD/MPV that arose de novo specifically on the maternally inherited chromosome and delete lung-specific lncRNA genes. These deletions define a distant cis-regulatory region that harbors, besides lncRNA genes, also a differentially methylated CpG island, binds GLI2 depending on the methylation status of this CpG island, and physically interacts with and up-regulates the FOXF1 promoter. We suggest that lung-transcribed 16q24.1 lncRNAs may contribute to long-range regulation of FOXF1 by GLI2 and other transcription factors. Perturbation of lncRNA-mediated chromatin interactions may, in general, be responsible for position effect phenomena and potentially cause many disorders of human development.

Szafranski, Przemyslaw; Dharmadhikari, Avinash V.; Brosens, Erwin; Gurha, Priyatansh; Kolodziejska, Katarzyna E.; Zhishuo, Ou; Dittwald, Piotr; Majewski, Tadeusz; Mohan, K. Naga; Chen, Bo; Person, Richard E.; Tibboel, Dick; de Klein, Annelies; Pinner, Jason; Chopra, Maya; Malcolm, Girvan; Peters, Gregory; Arbuckle, Susan; Guiang, Sixto F.; Hustead, Virginia A.; Jessurun, Jose; Hirsch, Russel; Witte, David P.; Maystadt, Isabelle; Sebire, Neil; Fisher, Richard; Langston, Claire; Sen, Partha; Stankiewicz, Pawel

2013-01-01

365

Small noncoding differentially methylated copy-number variants, including lncRNA genes, cause a lethal lung developmental disorder.  

PubMed

An unanticipated and tremendous amount of the noncoding sequence of the human genome is transcribed. Long noncoding RNAs (lncRNAs) constitute a significant fraction of non-protein-coding transcripts; however, their functions remain enigmatic. We demonstrate that deletions of a small noncoding differentially methylated region at 16q24.1, including lncRNA genes, cause a lethal lung developmental disorder, alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), with parent-of-origin effects. We identify overlapping deletions 250 kb upstream of FOXF1 in nine patients with ACD/MPV that arose de novo specifically on the maternally inherited chromosome and delete lung-specific lncRNA genes. These deletions define a distant cis-regulatory region that harbors, besides lncRNA genes, also a differentially methylated CpG island, binds GLI2 depending on the methylation status of this CpG island, and physically interacts with and up-regulates the FOXF1 promoter. We suggest that lung-transcribed 16q24.1 lncRNAs may contribute to long-range regulation of FOXF1 by GLI2 and other transcription factors. Perturbation of lncRNA-mediated chromatin interactions may, in general, be responsible for position effect phenomena and potentially cause many disorders of human development. PMID:23034409

Szafranski, Przemyslaw; Dharmadhikari, Avinash V; Brosens, Erwin; Gurha, Priyatansh; Kolodziejska, Katarzyna E; Zhishuo, Ou; Dittwald, Piotr; Majewski, Tadeusz; Mohan, K Naga; Chen, Bo; Person, Richard E; Tibboel, Dick; de Klein, Annelies; Pinner, Jason; Chopra, Maya; Malcolm, Girvan; Peters, Gregory; Arbuckle, Susan; Guiang, Sixto F; Hustead, Virginia A; Jessurun, Jose; Hirsch, Russel; Witte, David P; Maystadt, Isabelle; Sebire, Neil; Fisher, Richard; Langston, Claire; Sen, Partha; Stankiewicz, Pawe?

2012-10-03

366

Molecular cloning and chromosomal localization of the human [alpha][sub 7]-nicotinic receptor subunit gene (CHRNA7)  

SciTech Connect

The authors have isolated cDNA and genomic clones coding for the human [alpha][sub 7] neuronal nicotinic receptor subunit, the major component of brain nicotinic receptors that are blocked by [alpha]-bungarotoxin. The human [alpha][sub 7] neuronal nicotinic cDNA encodes a mature protein of 479 amino acids that is highly homologous to the rat [alpha][sub 7] neuronal nicotinic subunit (90%). The authors have mapped the human [alpha][sub 7]-nicotinic receptor subunit gene to chromosome 15, band q14, a region frequently rearranged in patients carrying a bisatellite 15 chromosome, large inv dup (15), whose clinical features include mental retardation and seizures. 15 refs., 2 figs.

Chini, B.; Raimond, E.; Moralli, D.; Balzaretti, M. (Dip. Genetica e Microbioligia, Pavia (Italy)); Elgoyhen, A.B.; Heinemann, S. (Salk Institute, La Jolla, CA (United States))

1994-01-15

367

Targeting the urokinase plasminogen activator receptor enhances gene transfer to human airway epithelia  

PubMed Central

Developing gene therapy for cystic fibrosis has been hindered by limited binding and endocytosis of vectors by human airway epithelia. Here we show that the apical membrane of airway epithelia express the urokinase plasminogen activator receptor (uPAR). Urokinase plasminogen activator (uPA), or a 7-residue peptide derived from this protein (u7-peptide), bound the receptor and stimulated apical endocytosis. Both ligands enhanced gene transfer by nonspecifically bound adenovirus and adeno-associated virus vectors and by a modified adenovirus vector that had been coupled to the u7-peptide. These data provide the first evidence that targeting an apical receptor can circumvent the two most important barriers to gene transfer in airway epithelia. Thus, the uPA/uPAR system may offer significant advantages for delivering genes and other pharmaceuticals to airway epithelia.

Drapkin, Paola T.; O'Riordan, Catherine R.; Yi, Su Min; Chiorini, John A.; Cardella, Jonathan; Zabner, Joseph; Welsh, Michael J.

2000-01-01

368

The mouse (Mus musculus) T cell receptor beta variable (TRBV), diversity (TRBD) and joining (TRBJ) genes.  

PubMed

'The Mouse (Mus musculus) T cell Receptor Beta Variable (TRBV), Diversity (TRBD), and Joining (TRBJ) Genes', the 14th report of the 'IMGT Locus in Focus' section, comprises 8 tables entitled: (1) 'Number of mouse (Mus musculus) germline TRBV genes at 6A-C and potential repertoire'; (2) 'Mouse (Mus musculus) germline TRBV genes at 6A-C'; (3) 'Mouse (Mus musculus) TRBV allele table'; (4) 'Mouse (Mus musculus) germline TRBD genes and alleles'; (5) 'Mouse (Mus musculus) germline TRBJ genes'; (6) 'Mouse (Mus musculus) TRBJ allele table'; (7) 'Correspondence between the different mouse (Mus musculus) TRBV gene nomenclatures'; (8) 'Mouse (Mus musculus) TRBV genes and related human TRBV genes'. These tables are available at the IMGT Marie-Paule page from IMGT, the international ImMunoGeneTics database (http://imgt.cines.fr:8104) created by Marie-Paule Lefranc, Université Montpellier II, CNRS, Montpellier, France. PMID:11096260

Bosc, N; Lefranc, M P

2000-01-01

369

Microsatellites in the Estrogen Receptor (ESR1, ESR2) and Androgen Receptor (AR) Genes and Breast Cancer Risk in African American and Nigerian Women  

Microsoft Academic Search

Genetic variants in hormone receptor genes may be crucial predisposing factors for breast cancer, and microsatellites in the estrogen receptor (ESR1, ESR2) and androgen receptor (AR) genes have been suggested to play a role. We studied 258 African-American (AA) women with breast cancer and 259 hospital-based controls, as well as 349 Nigerian (NG) female breast cancer patients and 296 community

Yonglan Zheng; Dezheng Huo; Jing Zhang; Toshio F. Yoshimatsu; Qun Niu; Olufunmilayo I. Olopade

2012-01-01

370

Mapping the human melanocortin 2 receptor (adrenocorticotropic hormone receptor; ACTHR) gene (MC2R) to the small arm of chromosome 18 (18p11. 21-pter)  

SciTech Connect

The human adrenocorticotropic hormone receptor (ACTHR) was recently cloned and shown to belong to the superfamily of membrane receptors that couple to guanine nucleotide-binding proteins and adenylyl cyclase. A genetically heterogeneous (including both X-linked and autosomally recessive forms) congenital syndrome of general hereditary adrenal unresponsiveness to ACTH has been documented in several kindreds. This inherited defect affects one of the steps in the cascade of events of ACTH action on glucocorticoid biosynthesis, without altering mineralocorticoid productions. Since candidate targets for pathophysiological manifestations of deficient responsiveness to ACTH include lesions of the ACTHR gene, the authors undertook to map it to a chromosomal location. They first used polymerase chain reaction (PCR) amplification of NIGMS Panel 1 DNA template to assign a 960-bp-long fragment of the human ACTHR gene to chromosome 18. Subsequently, they determined the location of the ACTHR gene within human chromosome 18 by PCR amplification of genomic DNA template from somatic cell hybrids that contain deletions of this chromosome.

Vamvakopoulos, N.C.; Chrousos, G.P. (National Institute of Child Health and Human Development, Bethesda, MD (United States)); Rojas, K.; Overhauser, J. (Thomas Jefferson Univ., Philadelphia, PA (United States)); Durkin, A.S.; Nierman, W.C. (American Type Collection, Rockville, MD (United States))

1993-11-01

371

Cloning and analysis of the gene encoding the human neonatal Fc receptor.  

PubMed

The neonatal Fc receptor, FcRn, is expressed in human placental syncytiotrophoblast, capillary endothelium, intestinal epithelium, and other tissues. By analogy with its role in the mouse, human FcRn is expected to transport maternal IgG to the foetus, and protect circulating IgG from catabolism. The larger subunit of FcRn is homologous to the alpha chains of the major histocompatibility complex (MHC) class I proteins, but is encoded outside the MHC on chromosome 19. We report the isolation of clones encoding the alpha chain of human FcRn from chromosome 19-specific libraries. The sequence revealed a similar organization to classical and non-classical MHC, and MHC-related genes. Compared with classical MHC class I genes, the human FcRn alpha chain gene has expanded by acquiring many repetitive sequences in its introns, including multiple Alu elements in the fourth intron. Primer extension analysis showed that there are two transcription initiation sites in the upstream flanking sequence. PMID:10998088

Mikulska, J E; Pablo, L; Canel, J; Simister, N E

2000-08-01

372

Dopamine D4 receptor gene associated with fairness preference in ultimatum game.  

PubMed

In experimental economics, the preference for reciprocal fairness has been observed in the controlled and incentivized laboratory setting of the ultimatum game, in which two individuals decide on how to divide a sum of money, with one proposing the share while the second deciding whether to accept. Should the proposal be accepted, the amount is divided accordingly. Otherwise, both would receive no money. A recent twin study has shown that fairness preference inferred from responder behavior is heritable, yet its neurogenetic basis remains unknown. The D4 receptor (DRD4) exon3 is a well-characterized functional polymorphism, which is known to be associated with attention deficit hyperactivity disorder and personality traits including novelty seeking and self-report altruism. Applying a neurogenetic approach, we find that DRD4 is significantly associated with fairness preference. Additionally, the interaction among this gene, season of birth, and gender is highly significant. This is the first result to link preference for reciprocal fairness to a specific gene and suggests that gene × environment interactions contribute to economic decision making. PMID:21072167

Zhong, Songfa; Israel, Salomon; Shalev, Idan; Xue, Hong; Ebstein, Richard P; Chew, Soo Hong

2010-11-03

373

Erythropoietin (EPO) Increases Myelin Gene Expression in CG4 Oligodendrocyte Cells through the Classical EPO Receptor.  

PubMed

Erythropoietin (EPO) has protective effects in neurodegenerative and neuroinflammatory diseases, including in animal models of multiple sclerosis, where EPO decreases disease severity. EPO also promotes neurogenesis and is protective in models of toxic demyelination. In this study, we asked whether EPO could promote neurorepair by also inducing remyelination. In addition, we investigated whether the effect of EPO could be mediated by the classical erythropoietic EPO receptor (EPOR), since it is still questioned if EPOR is functional in nonhematopoietic cells. Using CG4 cells, a line of rat oligodendrocyte precursor cells, we found that EPO increases the expression of myelin genes (myelin oligodendrocyte glycoprotein [MOG] and myelin basic protein [MBP]). EPO had no effect in wild-type CG4 cells, which do not express EPOR, whereas it increased MOG and MBP expression in cells engineered to overexpress EPOR (CG4-EPOR). This was reflected in a marked increase in MOG protein levels, as detected by Western blot. In these cells, EPO induced by 10-fold the early growth response gene 2 (Egr2), which is required for peripheral myelination. However, Egr2 silencing with a siRNA did not reverse the effect of EPO, indicating that EPO acts through other pathways. In conclusion, EPO induces the expression of myelin genes in oligodendrocytes and this effect requires the presence of EPOR. This study demonstrates that EPOR can mediate neuroreparative effects. PMID:23821361

Cervellini, Ilaria; Annenkov, Alexander; Brenton, Thomas; Chernajovsky, Yuti; Ghezzi, Pietro; Mengozzi, Manuela

2013-08-28

374

Dopamine D4 Receptor Gene Associated with Fairness Preference in Ultimatum Game  

PubMed Central

In experimental economics, the preference for reciprocal fairness has been observed in the controlled and incentivized laboratory setting of the ultimatum game, in which two individuals decide on how to divide a sum of money, with one proposing the share while the second deciding whether to accept. Should the proposal be accepted, the amount is divided accordingly. Otherwise, both would receive no money. A recent twin study has shown that fairness preference inferred from responder behavior is heritable, yet its neurogenetic basis remains unknown. The D4 receptor (DRD4) exon3 is a well-characterized functional polymorphism, which is known to be associated with attention deficit hyperactivity disorder and personality traits including novelty seeking and self-report altruism. Applying a neurogenetic approach, we find that DRD4 is significantly associated with fairness preference. Additionally, the interaction among this gene, season of birth, and gender is highly significant. This is the first result to link preference for reciprocal fairness to a specific gene and suggests that gene × environment interactions contribute to economic decision making.

Zhong, Songfa; Israel, Salomon; Shalev, Idan; Xue, Hong; Ebstein, Richard P.; Chew, Soo Hong

2010-01-01

375

Specific Chromosomal Aberrations and Amplification of the AIB1 Nuclear Receptor Coactivator Gene in Pancreatic Carcinomas  

PubMed Central

To screen pancreatic carcinomas for chromosomal aberrations we have applied molecular cytogenetic techniques, including fluorescent in situ hybridization, comparative genomic hybridization, and spectral karyotyping to a series of nine established cell lines. Comparative genomic hybridization revealed recurring chromosomal gains on chromosome arms 3q, 5p, 7p, 8q, 12p, and 20q. Chromosome losses were mapped to chromosome arms 8p, 9p, 17p, 18q, 19p, and chromosome 21. The comparison with comparative genomic hybridization data from primary pancreatic tumors indicates that a specific pattern of chromosomal copy number changes is maintained in cell culture. Metaphase chromosomes from six cell lines were analyzed by spectral karyotyping, a technique that allows one to visualize all chromosomes simultaneously in different colors. Spectral karyotyping identified multiple chromosomal rearrangements, the majority of which were unbalanced. No recurring reciprocal translocation was detected. Cytogenetic aberrations were confirmed using fluorescent in situ hybridization with probes for the MDR gene and the tumor suppressor genes p16 and DCC. Copy number increases on chromosome 20q were validated with a probe specific for the nuclear receptor coactivator AIB1 that maps to chromosome 20q12. Amplification of this gene was identified in six of nine pancreatic cancer cell lines and correlated with increased expression.

Ghadimi, B. Michael; Schrock, Evelin; Walker, Robert L.; Wangsa, Danny; Jauho, Annukka; Meltzer, Paul S.; Ried, Thomas

1999-01-01

376

Canonical Wnt/?-Catenin Regulation of Liver Receptor Homolog-1 Mediates Pluripotency Gene Expression  

PubMed Central

Delineating the signaling pathways that underlie ESC pluripotency is paramount for development of ESC applications in both the research and clinical settings. In culture pluripotency is maintained by leukemia inhibitory factor (LIF) stimulation of two separate signaling axes: Stat3/Klf4/Sox2 and PI3K/Tbx3/Nanog, which converge in the regulation of Oct4 expression. However, LIF signaling is not required in vivo for self-renewal, thus alternate signaling axes likely mediate these pathways. Additional factors that promote pluripotency gene expression have been identified, including the direct regulation of Oct4 by liver receptor homolog-1 (Lrh-1) and ?-catenin regulation of Nanog. Here, we present genetic, molecular, and pharmacological studies identifying a signaling axis in which ?-catenin promotes pluripotency gene expression in an Lrh-1-dependent manner. Furthermore, Lrh-1 was identified as a novel ?-catenin target gene, and Lrh-1 regulation is required for maintaining proper levels of Oct4, Nanog, and Tbx3. Elucidation of this pathway provides an alternate mechanism by which the primary pluripotency axis may be regulated in vivo and may pave the way for small molecule applications to manipulate pluripotency or improve the efficiency of somatic cell reprogramming. Stem Cells 2010;28:1794–1804

Wagner, Ryan T; Xu, Xueping; Yi, Fei; Merrill, Bradley J; Cooney, Austin J

2010-01-01

377

Erythropoietin (EPO) Increases Myelin Gene Expression in CG4 Oligodendrocyte Cells through the Classical EPO Receptor  

PubMed Central

Erythropoietin (EPO) has protective effects in neurodegenerative and neuroinflammatory diseases, including in animal models of multiple sclerosis, where EPO decreases disease severity. EPO also promotes neurogenesis and is protective in models of toxic demyelination. In this study, we asked whether EPO could promote neurorepair by also inducing remyelination. In addition, we investigated whether the effect of EPO could be mediated by the classical erythropoietic EPO receptor (EPOR), since it is still questioned if EPOR is functional in nonhematopoietic cells. Using CG4 cells, a line of rat oligodendrocyte precursor cells, we found that EPO increases the expression of myelin genes (myelin oligodendrocyte glycoprotein [MOG] and myelin basic protein [MBP]). EPO had no effect in wild-type CG4 cells, which do not express EPOR, whereas it increased MOG and MBP expression in cells engineered to overexpress EPOR (CG4-EPOR). This was reflected in a marked increase in MOG protein levels, as detected by Western blot. In these cells, EPO induced by 10-fold the early growth response gene 2 (Egr2), which is required for peripheral myelination. However, Egr2 silencing with a siRNA did not reverse the effect of EPO, indicating that EPO acts through other pathways. In conclusion, EPO induces the expression of myelin genes in oligodendrocytes and this effect requires the presence of EPOR. This study demonstrates that EPOR can mediate neuroreparative effects.

Cervellini, Ilaria; Annenkov, Alexander; Brenton, Thomas; Chernajovsky, Yuti; Ghezzi, Pietro; Mengozzi, Manuela

2013-01-01

378

Mutation screening of the Ectodysplasin-A receptor gene EDAR in hypohidrotic ectodermal dysplasia  

Microsoft Academic Search

Hypohidrotic ectodermal dysplasia (HED) can be caused by mutations in the X-linked ectodysplasin A (ED1) gene or the autosomal ectodysplasin A-receptor (EDAR) and EDAR-associated death domain (EDARADD) genes. X-linked and autosomal forms are sometimes clinically indistinguishable. For genetic counseling in families, it is therefore important to know the gene involved. In 24 of 42 unrelated patients with features of HED,

Annemarie H van der Hout; Grétel G Oudesluijs; Andrea Venema; Joke B G M Verheij; Bart G J Mol; Patrick Rump; Han G Brunner; Yvonne J Vos; Anthonie J van Essen

2008-01-01

379

Diversity of killer cell immunoglobulin-like receptor genes in four ethnic groups in China  

Microsoft Academic Search

Killer cell immunoglobulin-like receptors (KIRs) show extensive variation in terms of gene content and allelic polymorphisms\\u000a among different populations. The aim of this study was to analyze the distribution of KIR genes in the Bulang, Nu, Yugu, and\\u000a Zhuang ethnic groups, which belong to four different language families in China, and thus to provide basic KIR gene and genotype\\u000a data

Yufeng Yao; Lei Shi; Yufen Tao; Keqin Lin; Shuyuan Liu; Liang Yu; Zhaoqing Yang; Wen Yi; Xiaoqin Huang; Hao Sun; Jiayou Chu; Li Shi

380

Characterization of Melanocortin-1 Receptor Gene Variants in Uveal Melanoma Patients  

Microsoft Academic Search

PURPOSE. Allelic variations of the melanocortin-1 receptor (MC1R) gene have been linked to red hair and sun-sensitive skin types and may play a role in the susceptibility to develop cutaneous malignant melanoma (CMM). To define the role of MC1R gene in uveal melanoma, a case control study was performed, in which the presence of MC1R gene variations in uveal melanoma

Jessica A. W. Metzelaar-Blok; H. Monique; H. Hurks; Jan E. E. Keunen; Martine J. Jager; Nelleke A. Gruis

381

A multiexon deletion in the human low density lipoprotein receptor gene causes familial hypercholesterolemia  

SciTech Connect

Familial hypercholesterolemia (FH) is a widespread human disease. FH is caused by a disturbance in the catabolism of low density lipoproteins (LDL), which results from mutations in the LDL receptor gene (LDLR). The majority of mutations in the LDLR locus is represented by large-scale reorganizations in the above gene. In this study, we describe a novel 5 kb deletion, which eliminates exons 4 to 6 in the LDLR gene. 16 refs., 2 figs., 1 tab.

Mandel`shtam, M.Yu.; Lipovetskii, B.M.; Shvartsman, A.L.; Gaitskhoki, V.S. [Institute of Experimental Medicine, St. Petersburg (Russian Federation)

1995-02-01

382

Vitamin D Receptor Gene Polymorphism Affects Onset Pattern of Type 1 Diabetes  

Microsoft Academic Search

Type 1 diabetes mellitus is recognized as a T-cell-mediated autoimmune disease. Vitamin D compounds are known to sup- press T-cell activation by binding to the vitamin D receptor (VDR); and thus, VDR gene polymorphisms may be related to T-cell-mediated autoimmune diseases. We, therefore, investi- gated a VDR gene polymorphism in type 1 diabetes. We ex- amined the VDR gene Bsm

YOSHIKO MOTOHASHI; SATORU YAMADA; TATSUO YANAGAWA; TARO MARUYAMA; RYUJI SUZUKI; MASAAKI NIINO; TOSHIYUKI FUKAZAWA; AKIRA KASUGA; HIROSHI HIROSE; KOICHI MATSUBARA; AKIRA SHIMADA; TAKAO SARUTA

383

FSH receptor gene variants are rarely associated with premature ovarian failure.  

PubMed

FSH receptor (FSHR) gene variants have been associated with premature ovarian failure (POF). Genomic DNA from New Zealand women with POF (n=80) and control women (n=80) was screened for variants in FSHR exons 7 and 10. FSHR exon 7 variants, including the c.566C>T Finnish founder mutation (p.Ala189Val), were not detected. Previously reported FSHR exon 10 polymorphisms were identified in both groups with similar allelic distributions. A novel heterozygous FSHR exon 10 variant c.1411A>T, p.Ile471Phe was observed in one woman with a family history of POF, but not her affected siblings. It is concluded that variants in exons 7 and 10 of FSHR are not frequently associated with the development of POF in the New Zealand population. PMID:23419799

Woad, Kathryn J; Prendergast, Deborah; Winship, Ingrid M; Shelling, Andrew N

2013-01-19

384

Varenicline for Smoking Cessation: Nausea Severity and Variation in Nicotinic Receptor Genes  

PubMed Central

This study evaluated association between common and rare sequence variants in 10 nicotinic acetylcholine receptor subunit genes and the severity of nausea 21 days after initiating the standard, FDA-approved varenicline regimen for smoking cessation. Included in the analysis were 397 participants from a randomized clinical effectiveness trial with complete clinical and DNA resequencing data (mean age = 49.2 years; 68.0% female). Evidence for significant association between common sequence variants in CHRNB2 and nausea severity was obtained after adjusting for age, gender, and correlated tests (all PACT<.05). Individuals with the minor allele of CHRNB2 variants experienced less nausea than did those without the minor allele, consistent with previously reported findings for CHRNB2 and the occurrence of nausea and dizziness as a consequence of first smoking attempt in adolescents, and with the known neurophysiology of nausea. As nausea is the most common reason for discontinuance of varenicline, further pharmacogenetic investigations are warranted.

Swan, Gary E.; Javitz, Harold S.; Jack, Lisa M.; Wessel, Jennifer; Michel, Martha; Hinds, David A.; Stokowksi, Renee P.; McClure, Jennifer B.; Catz, Sheryl L.; Richards, Julie; Zbikowski, Susan M.; Deprey, Mona; McAfee, Tim; Conti, David V.; Bergen, Andrew W.

2012-01-01

385

Association Analysis of Exonic Variants of the GABA B Receptor Gene and Alpha Electroencephalogram Voltage in Normal Subjects and Alcohol-Dependent Patients  

Microsoft Academic Search

Based on pharmacologic evidence, it has been suggested that GABAB receptors may play a crucial role in the generation of alpha-electroencephalogram (EEG) oscillations. We tested whether three exonic variants of the gene encoding the human GABAB receptor (GABABR1) modify scalp-recorded alpha-EEG voltage. One hundred twenty-eight patients suffering from alcoholism and 114 normal subjects were investigated. Alcohol-dependent patients were included because

Georg Winterer; Richard Mahlberg; Michael N. Smolka; Jerzy Samochowiec; Mario Ziller; Hans-Peter Rommelspacher; Werner M. Herrmann; Lutz G. Schmidt; Thomas Sander

2003-01-01

386

Characterization of an Arabidopsis thaliana Gene that Defines a New Class of Putative Plant Receptor Kinases with an Extracellular Lectin-like Domain  

Microsoft Academic Search

We have characterized anArabidopsisreceptor-like serine\\/threonine kinase gene,Ath.lecRK1(Arabidopsis thalianalectin-receptor kinase), defining a new and putatively important class of plant receptor kinases. Structural features of the predicted polypeptide include an amino-terminal membrane-targeting signal sequence, a legume lectin-like extracellular domain, a single membrane-spanning domain, and a characteristic serine\\/threonine protein kinase domain. A recombinant protein containing the kinase domain can be autophosphorylated on a

C. Hervé; P. Dabos; J.-P. Galaud; P. Rougé; B. Lescure

1996-01-01

387

Histone methylation at gene promoters is associated with developmental regulation and region-specific expression of ionotropic and metabotropic glutamate receptors in human brain  

Microsoft Academic Search

Glutamatergic signaling is regulated, in part, through differential expression of NMDA and AMPA\\/KA channel subunits and G protein-coupled metabotropic receptors. In human brain, region-specific expression patterns of glutamate receptor genes are maintained over the course of decades, suggesting a role for molecular mechanisms involved in long-term regulation of transcription, including methylation of lysine residues at histone N-terminal tails. Using a

Florian Stadler; Gabriele Kolb; Lothar Rubusch; Stephen P. Baker; Edward G. Jones; Schahram Akbarian

2005-01-01

388

Olfactory Receptor-Gene Clusters, Genomic-Inversion Polymorphisms, and Common Chromosome Rearrangements  

PubMed Central

The olfactory receptor (OR)–gene superfamily is the largest in the mammalian genome. Several of the human OR genes appear in clusters with ?10 members located on almost all human chromosomes, and some chromosomes contain more than one cluster. We demonstrate, by experimental and in silico data, that unequal crossovers between two OR gene clusters in 8p are responsible for the formation of three recurrent chromosome macrorearrangements and a submicroscopic inversion polymorphism. The first two macrorearrangements are the inverted duplication of 8p, inv dup(8p), which is associated with a distinct phenotype, and a supernumerary marker chromosome, +der(8)(8p23.1pter), which is also a recurrent rearrangement and is associated with minor anomalies. We demonstrate that it is the reciprocal of the inv dup(8p). The third macrorearrangment is a recurrent 8p23 interstitial deletion associated with heart defect. Since inv dup(8p)s originate consistently in maternal meiosis, we investigated the maternal chromosomes 8 in eight mothers of subjects with inv dup(8p) and in the mother of one subject with +der(8), by means of probes included between the two 8p-OR gene clusters. All the mothers were heterozygous for an 8p submicroscopic inversion that was delimited by the 8p-OR gene clusters and was present, in heterozygous state, in 26% of a population of European descent. Thus, inversion heterozygosity may cause susceptibility to unequal recombination, leading to the formation of the inv dup(8p) or to its reciprocal product, the +der(8p). After the Yp inversion polymorphism, which is the preferential background for the PRKX/PRKY translocation in XX males and XY females, the OR-8p inversion is the second genomic polymorphism that confers susceptibility to the formation of common chromosome rearrangements. Accordingly, it may be possible to develop a profile of the individual risk of having progeny with chromosome rearrangements.

Giglio, Sabrina; Broman, Karl W.; Matsumoto, Naomichi; Calvari, Vladimiro; Gimelli, Giorgio; Neumann, Thomas; Ohashi, Hirofumi; Voullaire, Lucille; Larizza, Daniela; Giorda, Roberto; Weber, Jim L.; Ledbetter, David H.; Zuffardi, Orsetta

2001-01-01

389

Non-radioactive detection of immunoglobulin and T cell receptor gene rearrangement in acute lymphoblastic leukaemia.  

PubMed

Rearrangements of the heavy chain immunoglobulin gene and T cell receptor beta gene were investigated in 25 patients suffering from precursor B cell acute leukaemia and six patients suffering from T cell acute leukaemia using biotinylated DNA probes. All precursor B acute leukaemia patients had IgH gene rearrangements and 63% of those studied also had TCR beta gene rearrangements. All T cell acute leukaemia patients had TCR beta gene rearrangements and germline IgH configuration. Dilution experiments indicated that DNA from leukaemic cells representing 1-2% of a tested sample could be detected using this technique which compares favourably to radioactive DNA probes. PMID:1661125

Martin, G; Lawlor, E

1991-11-01

390

Increased Angiotensin II AT1 Receptor Expression in Paraventricular Nucleus and Hypothalamic-Pituitary-Adrenal Axis Stimulation in AT2 Receptor Gene Disrupted Mice  

Microsoft Academic Search

Angiotensin II AT2 receptor gene-disrupted mice have increased blood pressure and response to angiotensin II, behavioral alterations, greater response to stress, and increased adrenal AT1 receptors. We studied hypothalamic AT1 receptor binding and mRNA by receptor autoradiography and in situ hybridization, adrenal catecholamines by HPLC, adrenal tyrosine hydroxylase mRNA by in situ hybridization and pituitary and adrenal hormones by RIA

Inés Armando; José A. Terrón; Alicia Falcón-Neri; Ito Takeshi; Walter Häuser; Tadashi Inagami; Juan M. Saavedra

2002-01-01

391

Dexamethasone Stimulated Gene Expression in Peripheral Blood is a Sensitive Marker for Glucocorticoid Receptor Resistance in Depressed Patients  

PubMed Central

Although gene expression profiles in peripheral blood in major depression are not likely to identify genes directly involved in the pathomechanism of affective disorders, they may serve as biomarkers for this disorder. As previous studies using baseline gene expression profiles have provided mixed results, our approach was to use an in vivo dexamethasone challenge test and to compare glucocorticoid receptor (GR)-mediated changes in gene expression between depressed patients and healthy controls. Whole genome gene expression data (baseline and following GR-stimulation with 1.5?mg dexamethasone p.o.) from two independent cohorts were analyzed to identify gene expression pattern that would predict case and control status using a training (N=18 cases/18 controls) and a test cohort (N=11/13). Dexamethasone led to reproducible regulation of 2670 genes in controls and 1151 transcripts in cases. Several genes, including FKBP5 and DUSP1, previously associated with the pathophysiology of major depression, were found to be reliable markers of GR-activation. Using random forest analyses for classification, GR-stimulated gene expression outperformed baseline gene expression as a classifier for case and control status with a correct classification of 79.1 vs 41.6% in the test cohort. GR-stimulated gene expression performed best in dexamethasone non-suppressor patients (88.7% correctly classified with 100% sensitivity), but also correctly classified 77.3% of the suppressor patients (76.7% sensitivity), when using a refined set of 19 genes. Our study suggests that in vivo stimulated gene expression in peripheral blood cells could be a promising molecular marker of altered GR-functioning, an important component of the underlying pathology, in patients suffering from depressive episodes.

Menke, Andreas; Arloth, Janine; Putz, Benno; Weber, Peter; Klengel, Torsten; Mehta, Divya; Gonik, Mariya; Rex-Haffner, Monika; Rubel, Jennifer; Uhr, Manfred; Lucae, Susanne; Deussing, Jan M; Muller-Myhsok, Bertram; Holsboer, Florian; Binder, Elisabeth B

2012-01-01

392

The G protein coupled receptor Gpr153 shares common evolutionary origin with Gpr162 and is highly expressed in central regions including the thalamus, cerebellum and the arcuate nucleus.  

PubMed

The Rhodopsin family of G protein coupled receptors (GPCRs) includes the phylogenetic ?-group consisting of about 100 human members. The ?-group is the only group of GPCRs that has many receptors for biogenic amines which are major drug targets. Several members of this group are orphan receptors and their functions are elusive. In this study we present a detailed phylogenetic and anatomical characterization of the Gpr153 receptor and also attempt to study its functional role. We identified the homologue of Gpr153 in the elephant shark genome and phylogenetic and synteny analyses revealed that Gpr162 and Gpr153 share a common ancestor that split most likely through a duplication event before the divergence of the tetrapods and the teleost lineage. A quantitative real-time PCR study reveals widespread expression of Gpr153 in the central nervous system and all the peripheral tissues investigated. Detailed in?situ hybridization on mouse brain showed specifically high expression in the thalamus, cerebellum and the arcuate nucleus. The antisense oligodeoxynucleotide knockdown of Gpr153 caused a slight reduction in food intake and the elevated plus maze test showed significant reduction in the percentage of time spent in the centre square, which points towards a probable role in decision making. This report provides the first detailed characterization of the evolution, expression and primary functional properties of the Gpr153 gene. PMID:21981325

Sreedharan, Smitha; Almén, Markus S; Carlini, Valeria P; Haitina, Tatjana; Stephansson, Olga; Sommer, Wolfgang H; Heilig, Markus; de Barioglio, Susana R; Fredriksson, Robert; Schiöth, Helgi B

2011-10-31

393

Interleukin 1 receptor antagonist gene polymorphism association with lichen sclerosus  

Microsoft Academic Search

Cytokines play key roles in immune responses, inflammation and fibrosis. The balance between levels of cytokines, their receptors and specific inhibitors controls inflammatory reactions in tissues. The pathogenesis of lichen sclerosus is unknown but probably involves cytokine mediators such as interleukin 1 (IL-1) and interleukin 1 receptor antagonist (IL-1ra). The IL-1ra is a competitive inhibitor of IL-1a and IL-1ß, and

Frances E. Clay; Michael J. Cork; Joanna K. Tarlow; Alexandra I. F. Blakemore; Christine I. Harrington; Fiona Lewis; Gordon W. Duff

1994-01-01

394

The ERBB3 receptor in cancer and cancer gene therapy  

Microsoft Academic Search

ERBB3, a member of the epidermal growth factor receptor (EGFR) family, is unique in that its tyrosine kinase domain is functionally defective. It is activated by neuregulins, by other ERBB and nonERBB receptors as well as by other kinases, and by novel mechanisms. Downstream it interacts prominently with the phosphoinositol 3-kinase\\/AKT survival\\/mitogenic pathway, but also with GRB, SHC, SRC, ABL,

G Sithanandam; L M Anderson

2008-01-01

395

Effects of Vitamin A and D Receptor Gene Polymorphisms/Haplotypes on Immune Responses to Measles Vaccine  

PubMed Central

OBJECTIVE Vitamin A and D, and their receptors, are important regulators of the immune system, including vaccine immune response. We assessed the association between polymorphisms in the vitamin A (RARA, RARB and RARG) and vitamin D receptor (VDR)/RXRA genes and inter-individual variations in immune responses after two doses of measles vaccine in 745 subjects. METHODS Using a tagSNP approach, we genotyped 745 healthy children for the 391 polymorphisms in vitamin A and D receptor genes. RESULTS The RARB haplotype (rs6800566/rs6550976/rs9834818) was significantly associated with variations in both measles antibody (global p=0.013) and cytokine secretion levels, such as IL-10 (global p=0.006), IFN-? (global p=0.008), and TNF-? (global p=0.039) in the Caucasian subgroup. Specifically, the RARB haplotype AAC was associated with higher (t-statistic 3.27, p=0.001) measles antibody levels. At the other end of the spectrum, haplotype GG for rs6550978/rs6777544 was associated with lower antibody levels (t-statistic ?2.32, p=0.020) in the Caucasian subgroup. In a sensitivity analysis, the RARB haplotype CTGGGCAA remained marginally significant (p<0.02) when the single SNP rs12630816 was included in the model for IL-10 secretion levels. A significant association was found between lower measles-specific IFN-? Elispot responses and haplotypes rs11102986/rs11103473/rs11103482/rs10776909/rs12004589/rs35780541/rs2266677/rs875444 (global p=0.004) and rs6537944/rs3118571 (global p<0.001) in the RXRA gene for Caucasians. We also found associations between multiple RARB, VDR and RXRA SNPs/haplotypes and measles-specific IL-2, IL-6, IL-10, IFN-?, IFN-?, IFN?-1, and TNF-? cytokine secretion. CONCLUSION Our results suggest that specific allelic variations and haplotypes in the vitamin A and D receptor genes may influence adaptive immune responses to measles vaccine.

Ovsyannikova, Inna G.; Haralambieva, Iana H.; Vierkant, Robert A.; O'Byrne, Megan M.; Jacobson, Robert M.; Poland, Gregory A.

2011-01-01

396

Glucocorticoids, hippocampal corticosteroid receptor gene expression and antidepressant treatment: relationship with spatial learning in young and aged rats  

Microsoft Academic Search

The emergence of cognitive deficits in a subgroup of aged rats is associated with increased hypothalamic-pituitary-adrenal axis activity, decreased hippocampal mineralocorticoid and\\/or glucocorticoid receptor gene expression and neuronal loss. Short-term treatment with antidepressant drugs in young rats increases hippocampal corticosteroid receptor gene expression. In this study, the effects of chronic antidepressant administration on hippocampal mineralocorticoid and glucocorticoid receptor gene expression

J. L. W. Yau; T. Olsson; R. G. M. Morris; M. J. Meaney; J. R. Seckl

1995-01-01

397

Gene Deficiency in Activating Fc? Receptors Influences the Macrophage Phenotypic Balance and Reduces Atherosclerosis in Mice  

PubMed Central

Immunity contributes to arterial inflammation during atherosclerosis. Oxidized low-density lipoproteins induce an autoimmune response characterized by specific antibodies and immune complexes in atherosclerotic patients. We hypothesize that specific Fc? receptors for IgG constant region participate in atherogenesis by regulating the inflammatory state of lesional macrophages. In vivo we examined the role of activating Fc? receptors in atherosclerosis progression using bone marrow transplantation from mice deficient in ?-chain (the common signaling subunit of activating Fc? receptors) to hyperlipidemic mice. Hematopoietic deficiency of Fc? receptors significantly reduced atherosclerotic lesion size, which was associated with decreased number of macrophages and T lymphocytes, and increased T regulatory cell function. Lesions of Fc? receptor deficient mice exhibited increased plaque stability, as evidenced by higher collagen and smooth muscle cell content and decreased apoptosis. These effects were independent of changes in serum lipids and antibody response to oxidized low-density lipoproteins. Activating Fc? receptor deficiency reduced pro-inflammatory gene expression, nuclear factor-?B activity, and M1 macrophages at the lesion site, while increasing anti-inflammatory genes and M2 macrophages. The decreased inflammation in the lesions was mirrored by a reduced number of classical inflammatory monocytes in blood. In vitro, lack of activating Fc? receptors attenuated foam cell formation, oxidative stress and pro-inflammatory gene expression, and increased M2-associated genes in murine macrophages. Our study demonstrates that activating Fc? receptors influence the macrophage phenotypic balance in the artery wall of atherosclerotic mice and suggests that modulation of Fc? receptor-mediated inflammatory responses could effectively suppress atherosclerosis.

Mallavia, Benat; Oguiza, Ainhoa; Lopez-Franco, Oscar; Recio, Carlota; Ortiz-Munoz, Guadalupe; Lazaro, Iolanda; Lopez-Parra, Virginia; Egido, Jesus; Gomez-Guerrero, Carmen

2013-01-01

398

Activation of renal pelvic chemoreceptors in rats: role of calcitonin gene-related peptide receptors.  

PubMed

Substance P and calcitonin gene-related peptide (CGRP) increase afferent renal nerve activity (ARNA). A substance P receptor antagonist but not a CGRP receptor antagonist, h-CGRP (8-37), blocks the ARNA response to renal mechanoreceptor (MR) stimulation. We have examined whether calcitonin gene-related peptide activates renal pelvic sensory receptors and whether such activation contributes to renal chemoreceptor stimulation. The calcitonin gene-related peptide receptor antagonist, h-CGRP (8-37) [0.01-10 micromol L-1] dose-dependently decreased (29 +/- 4-86 +/- 13%, P < 0.01) the ipsilateral afferent renal nerve activity in response to the renal pelvic administration of calcitonin gene-related peptide (0.26 micromol L-1). Renal pelvic perfusion with 900 mM NaCl also increased ipsilateral ARNA (23 +/- 3% increase, P < 0.02) and contralateral urinary sodium excretion (13 +/- 4% increase, P < 0. 05). However, these responses to hypertonic NaCl were unaltered by h-CGRP (8-37). Renal pelvic perfusion with 1 or 10 microM h-CGRP (8-37) also failed to alter the ARNA responses to KCl (31.25, 62.5 and 125 mM). These results indicate that there are sensory receptors in the renal pelvic area that are responsive to calcitonin gene-related peptide. The activation of these receptors elicits a contralateral natriuretic response. In contrast, the activation of renal calcitonin gene-related peptide receptors does not contribute to renal chemoreceptor activation. PMID:10383496

Gontijo, J A; Kopp, U C

1999-06-01

399

The mating-type locus B alpha 1 of Schizophyllum commune contains a pheromone receptor gene and putative pheromone genes.  

PubMed Central

Analysis of the multispecific B alpha mating-type locus of Schizophyllum commune provided evidence that pheromones and pheromone receptors govern recognition of self versus non-self and sexual development in this homobasidiomycetous fungus. Four subclones of an 8.2 kb genomic fragment carrying B alpha 1 specificity induced B-regulated sexual morphogenesis when introduced into a strain with one of the eight compatible B alpha specificities that are known to exist in nature. One of these clones, which activated all other B alpha specificities, contains a gene termed bar1. The predicted protein product of bar1, as well as that of bar2, a homologous gene isolated from a B alpha 2 strain, has significant homology to known fungal pheromone receptor proteins in the rhodopsin-like superfamily of G protein-linked receptors. The other three active B alpha 1 clones were subcloned further to identify the minimal active element in each clone. Every active subclone contains a putative pheromone