Gabra2

Summary

Gene Symbol: Gabra2
Description: gamma-aminobutyric acid (GABA) A receptor, subunit alpha 2
Alias: C630048P16Rik, Gabra-2, gamma-aminobutyric acid receptor subunit alpha-2, GABA(A) receptor subunit alpha-2
Species: mouse
Products:     Gabra2

Top Publications

  1. Knabl J, Witschi R, Hösl K, Reinold H, Zeilhofer U, Ahmadi S, et al. Reversal of pathological pain through specific spinal GABAA receptor subtypes. Nature. 2008;451:330-4 pubmed publisher
    ..These results provide a rational basis for the development of subtype-selective GABAergic drugs for the treatment of chronic pain, which is often refractory to classical analgesics. ..
  2. Reynolds L, Engin E, Tantillo G, Lau H, Muschamp J, Carlezon W, et al. Differential roles of GABA(A) receptor subtypes in benzodiazepine-induced enhancement of brain-stimulation reward. Neuropsychopharmacology. 2012;37:2531-40 pubmed publisher
    ..This finding has important implications for the development of new medications that retain the therapeutic effects of benzodiazepines but lack abuse liability. ..
  3. Low K, Crestani F, Keist R, Benke D, Brünig I, Benson J, et al. Molecular and neuronal substrate for the selective attenuation of anxiety. Science. 2000;290:131-4 pubmed
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  4. Witschi R, Punnakkal P, Paul J, Walczak J, Cervero F, Fritschy J, et al. Presynaptic alpha2-GABAA receptors in primary afferent depolarization and spinal pain control. J Neurosci. 2011;31:8134-42 pubmed publisher
    ..Our results thus show that part of the antihyperalgesic action of spinally applied DZP occurs through facilitated activation of GABA(A) receptors residing on primary nociceptors. ..
  5. Dixon C, Morris H, Breen G, Desrivieres S, Jugurnauth S, Steiner R, et al. Cocaine effects on mouse incentive-learning and human addiction are linked to alpha2 subunit-containing GABAA receptors. Proc Natl Acad Sci U S A. 2010;107:2289-94 pubmed publisher
    ..Consistent with a role of these receptors in addiction, we found specific markers and haplotypes of the GABRA2 gene to be associated with human cocaine addiction.
  6. Kopp C, Rudolph U, Low K, Tobler I. Modulation of rhythmic brain activity by diazepam: GABA(A) receptor subtype and state specificity. Proc Natl Acad Sci U S A. 2004;101:3674-9 pubmed
    ....
  7. Ferraro T, Smith G, Schwebel C, Lohoff F, Furlong P, Berrettini W, et al. Quantitative trait locus for seizure susceptibility on mouse chromosome 5 confirmed with reciprocal congenic strains. Physiol Genomics. 2007;31:458-62 pubmed
    ....
  8. Nehrenberg D, Rodriguiz R, Cyr M, Zhang X, Lauder J, Gariepy J, et al. An anxiety-like phenotype in mice selectively bred for aggression. Behav Brain Res. 2009;201:179-91 pubmed publisher
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  9. Telegdy G, Schally A. Neurotransmitter-mediated action of an antagonist of growth hormone-releasing hormone on anxiolysis in mice. Behav Brain Res. 2012;233:232-6 pubmed publisher
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  10. Werner D, Swihart A, Rau V, Jia F, Borghese C, McCracken M, et al. Inhaled anesthetic responses of recombinant receptors and knockin mice harboring α2(S270H/L277A) GABA(A) receptor subunits that are resistant to isoflurane. J Pharmacol Exp Ther. 2011;336:134-44 pubmed publisher
    ..Thus, immobility or amnesia does not require isoflurane potentiation of the α2 subunit. ..

Detail Information

Publications62

  1. Knabl J, Witschi R, Hösl K, Reinold H, Zeilhofer U, Ahmadi S, et al. Reversal of pathological pain through specific spinal GABAA receptor subtypes. Nature. 2008;451:330-4 pubmed publisher
    ..These results provide a rational basis for the development of subtype-selective GABAergic drugs for the treatment of chronic pain, which is often refractory to classical analgesics. ..
  2. Reynolds L, Engin E, Tantillo G, Lau H, Muschamp J, Carlezon W, et al. Differential roles of GABA(A) receptor subtypes in benzodiazepine-induced enhancement of brain-stimulation reward. Neuropsychopharmacology. 2012;37:2531-40 pubmed publisher
    ..This finding has important implications for the development of new medications that retain the therapeutic effects of benzodiazepines but lack abuse liability. ..
  3. Low K, Crestani F, Keist R, Benke D, Brünig I, Benson J, et al. Molecular and neuronal substrate for the selective attenuation of anxiety. Science. 2000;290:131-4 pubmed
    ....
  4. Witschi R, Punnakkal P, Paul J, Walczak J, Cervero F, Fritschy J, et al. Presynaptic alpha2-GABAA receptors in primary afferent depolarization and spinal pain control. J Neurosci. 2011;31:8134-42 pubmed publisher
    ..Our results thus show that part of the antihyperalgesic action of spinally applied DZP occurs through facilitated activation of GABA(A) receptors residing on primary nociceptors. ..
  5. Dixon C, Morris H, Breen G, Desrivieres S, Jugurnauth S, Steiner R, et al. Cocaine effects on mouse incentive-learning and human addiction are linked to alpha2 subunit-containing GABAA receptors. Proc Natl Acad Sci U S A. 2010;107:2289-94 pubmed publisher
    ..Consistent with a role of these receptors in addiction, we found specific markers and haplotypes of the GABRA2 gene to be associated with human cocaine addiction.
  6. Kopp C, Rudolph U, Low K, Tobler I. Modulation of rhythmic brain activity by diazepam: GABA(A) receptor subtype and state specificity. Proc Natl Acad Sci U S A. 2004;101:3674-9 pubmed
    ....
  7. Ferraro T, Smith G, Schwebel C, Lohoff F, Furlong P, Berrettini W, et al. Quantitative trait locus for seizure susceptibility on mouse chromosome 5 confirmed with reciprocal congenic strains. Physiol Genomics. 2007;31:458-62 pubmed
    ....
  8. Nehrenberg D, Rodriguiz R, Cyr M, Zhang X, Lauder J, Gariepy J, et al. An anxiety-like phenotype in mice selectively bred for aggression. Behav Brain Res. 2009;201:179-91 pubmed publisher
    ....
  9. Telegdy G, Schally A. Neurotransmitter-mediated action of an antagonist of growth hormone-releasing hormone on anxiolysis in mice. Behav Brain Res. 2012;233:232-6 pubmed publisher
    ....
  10. Werner D, Swihart A, Rau V, Jia F, Borghese C, McCracken M, et al. Inhaled anesthetic responses of recombinant receptors and knockin mice harboring α2(S270H/L277A) GABA(A) receptor subunits that are resistant to isoflurane. J Pharmacol Exp Ther. 2011;336:134-44 pubmed publisher
    ..Thus, immobility or amnesia does not require isoflurane potentiation of the α2 subunit. ..
  11. Aguado F, Carmona M, Pozas E, Aguiló A, Martinez Guijarro F, Alcantara S, et al. BDNF regulates spontaneous correlated activity at early developmental stages by increasing synaptogenesis and expression of the K+/Cl- co-transporter KCC2. Development. 2003;130:1267-80 pubmed
    ..Given that BDNF itself is regulated by neuronal activity, we suggest that BDNF acts as a homeostatic factor controlling the emergence, complexity and networking properties of spontaneous networks. ..
  12. Bravo J, Forsythe P, Chew M, Escaravage E, Savignac H, Dinan T, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A. 2011;108:16050-5 pubmed publisher
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  13. Kwakowsky A, Schwirtlich M, Kooy F, Abrahám I, Mate Z, Katarova Z, et al. GABA neurotransmitter signaling in the developing mouse lens: dynamic regulation of components and functionality. Dev Dyn. 2008;237:3830-41 pubmed publisher
    ..The functionality of GABAR was verified by calcium imaging in whole lenses. Our data suggest that GABA synthesized locally by GAD, acts through GABA receptors by modulating the intracellular calcium levels. ..
  14. Duveau V, Laustela S, Barth L, Gianolini F, Vogt K, Keist R, et al. Spatiotemporal specificity of GABAA receptor-mediated regulation of adult hippocampal neurogenesis. Eur J Neurosci. 2011;34:362-73 pubmed publisher
    ..Taken together, the availability of distinct GABA(A) R subtypes provides a molecular mechanism endowing spatiotemporal specificity to GABAergic control of neuronal maturation in adult brain. ..
  15. Bähner F, Weiss E, Birke G, Maier N, Schmitz D, Rudolph U, et al. Cellular correlate of assembly formation in oscillating hippocampal networks in vitro. Proc Natl Acad Sci U S A. 2011;108:E607-16 pubmed publisher
    ..Ectopic spike generation together with strong somatodendritic inhibition may provide a cellular mechanism for the definition of oscillating assemblies. ..
  16. Mo J, Kim C, Lee D, Sun W, Lee H, Kim H. Early growth response 1 (Egr-1) directly regulates GABAA receptor α2, α4, and θ subunits in the hippocampus. J Neurochem. 2015;133:489-500 pubmed publisher
    ..PCR approach, in combination with in vivo chromatin immunoprecipitation, and reveals that GABAA receptor subunit, GABRA2 (α2), GABRA4 (α4), and GABRQ (θ) genes, are transcriptional targets of Egr-1...
  17. Maison S, Rosahl T, Homanics G, Liberman M. Functional role of GABAergic innervation of the cochlea: phenotypic analysis of mice lacking GABA(A) receptor subunits alpha 1, alpha 2, alpha 5, alpha 6, beta 2, beta 3, or delta. J Neurosci. 2006;26:10315-26 pubmed
    ..Results suggest that the GABAergic component of the olivocochlear system contributes to the long-term maintenance of hair cells and neurons in the inner ear. ..
  18. Gill K, Boyle A. Quantitative trait loci for novelty/stress-induced locomotor activation in recombinant inbred (RI) and recombinant congenic (RC) strains of mice. Behav Brain Res. 2005;161:113-24 pubmed
    ..The results are discussed in the context of previous QTL studies of anxiety-related traits that have used genetic crosses that include the A or B6 progenitors. ..
  19. Fritschy J, Johnson D, Mohler H, Rudolph U. Independent assembly and subcellular targeting of GABA(A)-receptor subtypes demonstrated in mouse hippocampal and olfactory neurons in vivo. Neurosci Lett. 1998;249:99-102 pubmed
    ..These findings indicate that the assembly of distinct GABA(A)-receptor subtypes in the same neuron is regulated independently. Furthermore, the alpha-subunit is a prime candidate for providing domains which direct subcellular targeting. ..
  20. Ghosh H, Auguadri L, Battaglia S, Simone Thirouin Z, Zemoura K, Messner S, et al. Several posttranslational modifications act in concert to regulate gephyrin scaffolding and GABAergic transmission. Nat Commun. 2016;7:13365 pubmed publisher
    ..expression of SUMOylation-deficient gephyrin variants rescued gephyrin clustering in CA1 or neocortical neurons of Gabra2-null mice, which otherwise lack gephyrin clusters, indicating that gephyrin SUMO modification is an essential ..
  21. Tsuchiya H, Oka T, Nakamura K, Ichikawa A, Saper C, Sugimoto Y. Prostaglandin E2 attenuates preoptic expression of GABAA receptors via EP3 receptors. J Biol Chem. 2008;283:11064-71 pubmed publisher
    ..These results indicate that PGE(2)-EP3 signaling elicits G(i/o) activation in preoptic thermocenter neurons, and we propose the possibility that a rapid decrease in preoptic GABA(A) expression may be involved in PGE(2)-induced fever. ..
  22. Buckle V, Fujita N, Ryder Cook A, Derry J, Barnard P, Lebo R, et al. Chromosomal localization of GABAA receptor subunit genes: relationship to human genetic disease. Neuron. 1989;3:647-54 pubmed
    ..The combined results locate the human alpha 3 gene within band Xq28, in a location that makes it a candidate gene for the X-linked form of manic depression. ..
  23. Lu L, Airey D, Williams R. Complex trait analysis of the hippocampus: mapping and biometric analysis of two novel gene loci with specific effects on hippocampal structure in mice. J Neurosci. 2001;21:3503-14 pubmed
    ..The Hipp gene loci modulate neuron number in the dentate gyrus, collectively shifting the population up or down by as much as 200,000 cells. Candidate genes for the Hipp loci include Rxrg and Fgfr3. ..
  24. Quadrato G, Elnaggar M, Duman C, Sabino A, Forsberg K, Di Giovanni S. Modulation of GABAA receptor signaling increases neurogenesis and suppresses anxiety through NFATc4. J Neurosci. 2014;34:8630-45 pubmed publisher
    ..receptor (GABAAR) signaling modulates hippocampal neurogenesis through NFATc4 activity, which in turn regulates GABRA2 and GABRA4 subunit expression via binding to specific promoter responsive elements, as assessed by ChIP and ..
  25. Chang C, Luntz Leybman V, Evans J, Rotter A, Frostholm A. Developmental changes in the expression of gamma-aminobutyric acidA/benzodiazepine receptor subunit mRNAs in the murine inferior olivary complex. J Comp Neurol. 1995;356:615-28 pubmed
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  26. Nagle D, Kozak C, Mano H, Chapman V, Bucan M. Physical mapping of the Tec and Gabrb1 loci reveals that the Wsh mutation on mouse chromosome 5 is associated with an inversion. Hum Mol Genet. 1995;4:2073-9 pubmed
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  27. Fagiolini M, Fritschy J, Löw K, Mohler H, Rudolph U, Hensch T. Specific GABAA circuits for visual cortical plasticity. Science. 2004;303:1681-3 pubmed
    ..This dissociation carries implications for models of brain development and the safe design of benzodiazepines for use in infants. ..
  28. Lee G, Gammie S. GABAA receptor signaling in caudal periaqueductal gray regulates maternal aggression and maternal care in mice. Behav Brain Res. 2010;213:230-7 pubmed publisher
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  29. Hawkins N, Zachwieja N, Miller A, Anderson L, Kearney J. Fine Mapping of a Dravet Syndrome Modifier Locus on Mouse Chromosome 5 and Candidate Gene Analysis by RNA-Seq. PLoS Genet. 2016;12:e1006398 pubmed publisher
    ..differences between 129S6/SvEvTac and [129xC57BL/6J]F1 were identified, including the GABAA receptor subunit, Gabra2. Further analysis of Gabra2 demonstrated allele-specific expression...
  30. Lim C, Kim H, Yu N, Kang S, Kim T, Ko H, et al. Enhancing inhibitory synaptic function reverses spatial memory deficits in Shank2 mutant mice. Neuropharmacology. 2017;112:104-112 pubmed publisher
    ..Here, we found that the expression levels of Gabra2, as well as of GABA receptor-mediated inhibitory neurotransmission, are reduced in Shank2 e6-7, but not in e7 KO ..
  31. Bailey S, Toth M. Variability in the benzodiazepine response of serotonin 5-HT1A receptor null mice displaying anxiety-like phenotype: evidence for genetic modifiers in the 5-HT-mediated regulation of GABA(A) receptors. J Neurosci. 2004;24:6343-51 pubmed
    ..These data indicate that BZ-resistant anxiety results from a developmental arrest of GABA(A)R expression in SW-R-/- mice, and a similar mechanism may be responsible for the BZ insensitivity of some anxiety patients. ..
  32. Wang J, Kofuji P, Fernando J, Moss S, Huganir R, Burt D. The alpha 1, alpha 2, and alpha 3 subunits of GABAA receptors: comparison in seizure-prone and -resistant mice and during development. J Mol Neurosci. 1992;3:177-84 pubmed
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  33. Khrestchatisky M, MacLennan A, Tillakaratne N, Chiang M, Tobin A. Sequence and regional distribution of the mRNA encoding the alpha 2 polypeptide of rat gamma-aminobutyric acidA receptors. J Neurochem. 1991;56:1717-22 pubmed
    ..The distribution of alpha 2 mRNAs in rat brain suggests that the alpha 2 subunit may indeed be involved in the BZ type II receptors. ..
  34. Reddy D, Gangisetty O, Wu X. PR-independent neurosteroid regulation of α2-GABA-A receptors in the hippocampus subfields. Brain Res. 2017;1659:142-147 pubmed publisher
    ..These findings suggest that ovarian cycle-related P and neurosteroids regulate α2-GABA-A receptor expression in the hippocampus via a non-PR pathway, which may be relevant to menstrual-cycle related brain conditions. ..
  35. Newman E, Gunner G, Huynh P, Gachette D, Moss S, Smart T, et al. Effects of Gabra2 Point Mutations on Alcohol Intake: Increased Binge-Like and Blunted Chronic Drinking by Mice. Alcohol Clin Exp Res. 2016;40:2445-2455 pubmed publisher
    Alcohol use disorders are associated with single-nucleotide polymorphisms in GABRA2, the gene encoding the GABAA receptor α2-subunit in humans...
  36. Kasugai Y, Swinny J, Roberts J, Dalezios Y, Fukazawa Y, Sieghart W, et al. Quantitative localisation of synaptic and extrasynaptic GABAA receptor subunits on hippocampal pyramidal cells by freeze-fracture replica immunolabelling. Eur J Neurosci. 2010;32:1868-88 pubmed publisher
    ..Assuming similar antibody access to all receptors, about 60% of these subunits are in extrasynaptic receptors. ..
  37. Yamanaka S, Johnson O, Lyu M, Kozak C, Proia R. The mouse gene encoding the GM2 activator protein (Gm2a): cDNA sequence, expression, and chromosome mapping. Genomics. 1994;24:601-4 pubmed
    ..The Gm2a gene was mapped to a region on mouse chromosome (Chr) 11 that is homologous with a segment of human chromosome 5 containing the orthologous human gene. In addition, a Gm2a-related sequence (Gm2a-rs1) was mapped to mouse Chr 5. ..
  38. Chen R, Zhang Q, Duan X, York P, Chen G, Yin P, et al. The 5-Hydroxymethylcytosine (5hmC) Reader UHRF2 Is Required for Normal Levels of 5hmC in Mouse Adult Brain and Spatial Learning and Memory. J Biol Chem. 2017;292:4533-4543 pubmed publisher
    ..Together, our study supports UHRF2 as a bona fide 5hmC reader and further demonstrates a role for 5hmC in neuronal function. ..
  39. Bedford F, Kittler J, Muller E, Thomas P, Uren J, Merlo D, et al. GABA(A) receptor cell surface number and subunit stability are regulated by the ubiquitin-like protein Plic-1. Nat Neurosci. 2001;4:908-16 pubmed
    ..Our study identifies a previously unknown role for Plic-1, a modulation of GABA(A) receptor cell surface number, which suggests that Plic-1 facilitates accumulation of these receptors in dendritic membranes. ..
  40. Marowsky A, Fritschy J, Vogt K. Functional mapping of GABA A receptor subtypes in the amygdala. Eur J Neurosci. 2004;20:1281-9 pubmed
    ..The crucial role of the amygdala for the mediation of anxiety is in agreement with the part that alpha2-subunit-containing GABA A receptors play in anxiolysis and their important function in this area of the brain. ..
  41. Paul J, Yevenes G, Benke D, Di Lio A, Ralvenius W, Witschi R, et al. Antihyperalgesia by α2-GABAA receptors occurs via a genuine spinal action and does not involve supraspinal sites. Neuropsychopharmacology. 2014;39:477-87 pubmed publisher
    ..Such drugs may therefore be well-suited for the systemic treatment of different chronic pain conditions. ..
  42. Engin E, Zarnowska E, Benke D, Tsvetkov E, Sigal M, Keist R, et al. Tonic Inhibitory Control of Dentate Gyrus Granule Cells by α5-Containing GABAA Receptors Reduces Memory Interference. J Neurosci. 2015;35:13698-712 pubmed publisher
    ..Thus, the findings link interference management to a specific mechanism, proposed previously by computational models. ..
  43. Wang L, Nomura M, Goto Y, Tanaka K, Sakamoto R, Abe I, et al. Smad2 protein disruption in the central nervous system leads to aberrant cerebellar development and early postnatal ataxia in mice. J Biol Chem. 2011;286:18766-74 pubmed publisher
    ..These findings indicate that Smad2 plays a key role in cerebellar development and motor function control. ..
  44. Telegdy G, Schally A. Involvement of neurotransmitters in the action of growth hormone-releasing hormone antagonist on passive avoidance learning. Behav Brain Res. 2012;233:326-30 pubmed publisher
    ..The results demonstrate that the muscarinic acetylcholine receptor, the 5-HT1/5-HT2 serotonergic receptor and opioid receptors are involved as mediators in the action of MZ-4-71 on the consolidation of passive avoidance learning. ..
  45. Peden D, Petitjean C, Herd M, Durakoglugil M, Rosahl T, Wafford K, et al. Developmental maturation of synaptic and extrasynaptic GABAA receptors in mouse thalamic ventrobasal neurones. J Physiol. 2008;586:965-87 pubmed
    ..Changes to synaptic GABA(A) receptor function and the increased expression of extrasynaptic GABA(A) receptors represent two distinct mechanisms for fine-tuning GABA-ergic control of thalamic relay neurone activity during development. ..
  46. Prenosil G, Schneider Gasser E, Rudolph U, Keist R, Fritschy J, Vogt K. Specific subtypes of GABAA receptors mediate phasic and tonic forms of inhibition in hippocampal pyramidal neurons. J Neurophysiol. 2006;96:846-57 pubmed
    ..These results show that the major forms of inhibitory neurotransmission in hippocampal pyramidal cells are mediated by distinct GABA(A)Rs subtypes...
  47. Temple J, Wray S. Developmental changes in GABA receptor subunit composition within the gonadotrophin-releasing hormone-1 neuronal system. J Neuroendocrinol. 2005;17:591-9 pubmed
    ..5 to adulthood, as well as in nasal explants. We show that GABAAalpha2 and alpha6 are present in the GnRH-1 neuronal system both in vivo and in vitro and that the levels of expression are altered as a function of age. ..
  48. Blednov Y, Benavidez J, Black M, Chandra D, Homanics G, Rudolph U, et al. Linking GABA(A) receptor subunits to alcohol-induced conditioned taste aversion and recovery from acute alcohol intoxication. Neuropharmacology. 2013;67:46-56 pubmed publisher
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  49. Benham R, Hewage N, Suckow R, Engin E, Rudolph U. Prodepressant- and anxiogenic-like effects of serotonin-selective, but not noradrenaline-selective, antidepressant agents in mice lacking α2-containing GABAA receptors. Behav Brain Res. 2017;332:172-179 pubmed publisher
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