The human γ-aminobutyric acid A receptor delta (GABRD) gene: molecular characterisation and tissue-specific expression

Windpassinger, Christian; Kroisel, Peter M.; Wagner, Klaus; Petek, Erwin

doi:10.1016/s0378-1119(02)00649-2

Cited by 66 publications

(53 citation statements)

References 12 publications

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“…We have confirmed in the genome that this gene is in 1p36.3, but only eight exons are currently annotated as such in data bases, with seven of these in full agreement with the last seven exons reported in Ref. 46. First, by BLASTN search of the genome with cDNA sequences covering the other four reported exons, we found in the GABRD gene that a noncoding exon is indeed present in the 5Ј-utr, being in fact the first exon of the gene; this corresponds to the reported (46) GABRD "1B" sequence (except for the first 12 nucleotides of 1B, which are not present in the GABRD gene).…”

Section: Locations and Clusters Of All Gaba A Receptor Genessupporting

confidence: 87%

“…It was located in band p36.3 by Windpassinger et al (46), who also obtained cDNA sequences to deduce that it has 11 exons, 10 of which are coding. Three of these were proposed to be expressed alternatively, although three corresponding subunit cDNAs were not isolated from tissues.…”

Section: Locations and Clusters Of All Gaba A Receptor Genesmentioning

confidence: 99%

“…Second, exon 2 of GABRD starts with the sequence of the "5Ј-variant exon 1C" of Ref. 46, which contains a further 301 bp of 5Ј-utr and then encodes the initial 37 amino acids including the signal peptide. However, there is no adjacent intron following, and exon 2 in fact continues with a further 115 bp that encode the next 39 amino acids.…”

Section: Locations and Clusters Of All Gaba A Receptor Genesmentioning

confidence: 99%

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Analysis of the Set of GABAA Receptor Genes in the Human Genome

Simon

Wakimoto

Fujita

et al. 2004

Journal of Biological Chemistry

233

196

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The genes of the ionotropic ␥-aminobutyric acid receptor (GABR) subunits have shown an unusual chromosomal clustering, but only now can this be fully specified by analyses of the human genome. We have characterized the genes encoding the 18 known human GABR subunits, plus one now located here, for their precise locations, sizes, and exon/intron structures. Clusters of 17 of the 19, distributed between five chromosomes, are specified in detail, and their possible significance is considered. By applying search algorithms designed to recognize sequences of all known GABRtype subunits in species from man down to nematodes, we found no new GABR subunit is detectable in the human genome. However, the sequence of the human orthologue of the rat GABR 3 receptor subunit was uncovered by these algorithms, and its gene could be analyzed. Consistent with those search results, orthologues of the ␤4 and ␥4 subunits from the chicken, not cloned from mammals, were not detectable in the human genome by specific searches for them. The relationships are consistent with the mammalian subunit being derived from the ␤ line and ⑀ from the ␥ line, with mammalian loss of ␤4 and ␥4. In their structures the human GABR genes show a basic pattern of nine coding exons, with six different genomic mechanisms for the alternative splicing found in various subunits. Additional noncoding exons occur for certain subunits, which can be regulatory. A dicysteine loop and its exon show remarkable constancy between all GABR subunits and species, of deduced functional significance.

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Section: Locations and Clusters Of All Gaba A Receptor Genessupporting

confidence: 87%

Section: Locations and Clusters Of All Gaba A Receptor Genesmentioning

confidence: 99%

Section: Locations and Clusters Of All Gaba A Receptor Genesmentioning

confidence: 99%

See 1 more Smart Citation

Analysis of the Set of GABAA Receptor Genes in the Human Genome

Simon

Wakimoto

Fujita

et al. 2004

Journal of Biological Chemistry

233

196

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“…Interestingly, ablation of the δ subunit results in reduced fertility. Unlike mice, ablation of the δ subunit in human beings may associated with abnormalities caused by terminal deletions of 1p36 (Windpassinger et al, 2002). These authors have mapped the human GABA A δ subunit to 1p36.33.…”

Section: Gaba a Receptor Expression During Embryonic Developmentmentioning

confidence: 99%

Neurosteroid regulation of central nervous system development

Mellon

2007

Pharmacology & Therapeutics

186

117

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Neurosteroids are a relatively new class of neuroactive compounds, brought to prominence in the past two decades. Despite knowing of their presence in the nervous system of various species for over twenty years and knowing of their functions as GABA A and NMDA ligands, new and unexpected functions of these compounds are continuously being identified. Absence or reduced concentrations of neurosteroids during development and in adults may be associated with neurodevelopmental, psychiatric, or behavioral disorders. Treatment with physiologic or pharmacologic concentrations of these compounds may also promote neurogenesis, neuronal survival, myelination, increased memory, and reduced neurotoxicity. This review highlights what is currently known about the neurodevelopmental functions and mechanisms of action of four distinct neurosteroids -pregnenolone, progesterone, allopregnanolone and dehydroepiandrosterone.

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“…GABA A Rs containing a d-subunit, rather than a g-subunit, are more sensitive to neurosteroids (Belelli et al, 2002), and mice lacking GABA A d-subunits are less sensitive to neurosteroids (Brown et al, 2002;Mihalek et al, 1999Mihalek et al, , 2001Stell et al, 2003;Wohlfarth et al, 2002). This may account for the abnormal behavior of patients with 1q36 deletion, which includes the human GABA A d-subunit gene (Windpassinger et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

DHEA Lessens Depressive-Like Behavior via GABA-ergic Modulation of the Mesolimbic System

Genud

Merenlender

Gispan-Herman

et al. 2008

Neuropsychopharmacol

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Alterations in the levels of dehydroepiandrosterone (DHEA) in the brain can allosterically modulate g-aminobutyric-acid-type-A (GABA A R), N-methyl-D-aspartate (NMDAR), and Sigma-1 (s1R) receptors. In humans, DHEA has antidepressive effects; however, the mechanism is unknown. We examined whether alterations in DHEA also occur in an animal model of depression, the Flinders-sensitiveline (FSL) rats, with the intention of determining the brain site of DHEA action and its antidepressant mechanism. We discovered that DHEA levels were lower in some brain regions involved with depression of FSL rats compared to Sprague-Dawley (SD) controls. Moreover, DHEA (1 mg/kg IP for 14 days)-treated FSL rats were more mobile in the forced swim test than FSL controls. In the NAc and VTA, significant changes were observed in the levels of the d-subunit of GABA A , but not of s1R mRNA, in FSL rats compared to SD rats. The d-subunit controls the sensitivity of the GABA A R to the neurosteroid. Indeed, treatment (14 days) of FSL rats with the GABA A agonist muscimol (0.5 mg/kg), together with DHEA (a negative modulator of GABA A ), reversed the effect of DHEA on immobility in the swim test. Perfusion of DHEA sulfate (DHEAS) (3 nM and 30 nM for 14 days) into the VTA and NAc of FSL rats improved their performance in the swim test for at least 3 weeks post-treatment. Our results imply that alterations in DHEA are involved in the pathophysiology of depression and that the antidepressant action of DHEA is mediated via GABA A Rs in the NAc and VTA.

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The human γ-aminobutyric acid A receptor delta (GABRD) gene: molecular characterisation and tissue-specific expression

Cited by 66 publications

References 12 publications

Analysis of the Set of GABAA Receptor Genes in the Human Genome

Analysis of the Set of GABAA Receptor Genes in the Human Genome

Neurosteroid regulation of central nervous system development

DHEA Lessens Depressive-Like Behavior via GABA-ergic Modulation of the Mesolimbic System

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