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Gabrg2  -  gamma-aminobutyric acid (GABA) A receptor,...

Mus musculus

Synonyms: AI851231, BB128510, GABA(A) receptor subunit gamma-2, GABAA-R, Gabrg-2, ...
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Disease relevance of Gabrg2


Psychiatry related information on Gabrg2

  • The gamma2 +/- mice showed enhanced behavioral inhibition toward natural aversive stimuli and heightened responsiveness in trace fear conditioning and ambiguous cue discrimination learning [5].

High impact information on Gabrg2

  • This hypothesis inevitably postulates the gene order 5'-gamma 1-gamma 3-psi gamma-3'. Cloning of overlapping chromosomal segments demonstrates that the gamma 2 gene is located 19 kb 5' to the gamma 4 gene [6].
  • We have determined the order of the mouse immunoglobulin gamma 1, gamma 2 b, gamma 2 a and epsilon genes by molecular cloning of overlapping chromosomal segments [7].
  • GABAA receptors consisting of the alpha 1 and beta 1 or the alpha 1, beta 1, and gamma 2 subunits were directly phosphorylated on the beta 1 subunit by adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase (PKA) [8].
  • However, ZFP54 virtually abolished both gamma2 and gamma1 expression, and completely blocked adipogenesis [9].
  • To determine functional differences between the two splice variants of PPARgamma (gamma1 and gamma2), we sought to selectively repress gamma2 expression by targeting engineered zinc finger repressor proteins (ZFPs) to the gamma2-specific promoter, P2 [9].

Chemical compound and disease context of Gabrg2


Biological context of Gabrg2

  • The alcohol-related phenotypes associated with Gabrg2 generally may be characterized as debilitating or motivationally negative [1].
  • Nova regulates GABA(A) receptor gamma2 alternative splicing via a distal downstream UCAU-rich intronic splicing enhancer [14].
  • This polymorphism predicts a difference in amino acid sequence (Ala-11 vs. Thr-11) within the extracellular amino-terminal region of the gamma2 subunit [15].
  • Knockdown mice, on average, showed a 65% reduction of gamma2 subunit mRNA compared to controls; however gamma2 gene expression was highly variable in these mice, ranging from 10-95% of normal [16].
  • Targeted disruption of the GABA(A) receptor delta subunit gene leads to an up-regulation of gamma 2 subunit-containing receptors in cerebellar granule cells [17].

Anatomical context of Gabrg2


Associations of Gabrg2 with chemical compounds

  • Glucose dose-dependently increased GABA(A)R expression in both islets and alphaTC1-9 cells such that mRNA levels at 16 mmol/l glucose were approximately 3.0-fold (alpha4), 2.0-fold (beta3), or 1.5-fold (gamma2) higher than at basal glucose concentrations (2.5 or 1.0 mmol/l, respectively) [20].
  • Deletion of the gamma2 subunit in the third postnatal week resulted in loss of benzodiazepine-binding sites and parallel loss of punctate immunoreactivity for postsynaptic GABA(A) receptors and gephyrin [22].
  • The gamma2 subunit of GABA(A) receptor chloride channels is required for normal channel function and for postsynaptic clustering of these receptors during synaptogenesis [22].
  • Acute ethanol injection resulted in increased expression of alpha 1 and beta 3 mRNAs, whereas levels of alpha 6, beta 2, and gamma 2 mRNAs remained stable [23].
  • Glycine receptors and GABA receptor alpha 1 and gamma 2 subunits during the development of mouse hypoglossal nucleus [24].

Physical interactions of Gabrg2

  • GABA(A) receptors (GABA(A)Rs) containing the gamma2 subunit are thought to require the interacting protein GABARAP (GABA(A)R associated protein) for trafficking to the neuronal plasma membrane [25].
  • Hence, both C gamma 2 and C gamma 3 seem to be required for binding to Fc gamma RII, but the C gamma 1-hinge region has no detectable effect [26].
  • We also establish that the tyrosine kinase Src is capable of specifically interacting with the intracellular domains of receptor beta and gamma2 subunits [27].

Co-localisations of Gabrg2

  • Moreover, the gamma3 subunit can substitute for gamma2 in the formation of GABA(A) receptors that are synaptically clustered and colocalized with gephyrin in vivo [28].

Regulatory relationships of Gabrg2


Other interactions of Gabrg2

  • Here, we have biochemically confirmed the observation that splicing regulation of the inhibitory GABA(A) receptor gamma2 (GABA(A)Rgamma2) subunit pre-mRNA exon E9 is disrupted in mice lacking Nova-1 [14].
  • RESULTS: Allelic variation in Gabrg2 is correlated genetically with predisposition to acute alcohol withdrawal and may underlie the Alcw3 locus [1].
  • A previous study (Kneussel et al., 1999) reported a complete loss of synaptic clusters of the major GABA(A)R subunits alpha2 and gamma2 in hippocampal neurons lacking gephyrin [34].
  • The gamma2 subunit of GABA(A) receptors is a substrate for palmitoylation by GODZ [35].
  • GABAA receptor gamma 2 subunit knockdown mice have enhanced anxiety-like behavior but unaltered hypnotic response to benzodiazepines [16].

Analytical, diagnostic and therapeutic context of Gabrg2


  1. Allelic variation in the GABA A receptor gamma2 subunit is associated with genetic susceptibility to ethanol-induced motor incoordination and hypothermia, conditioned taste aversion, and withdrawal in BXD/Ty recombinant inbred mice. Hood, H.M., Buck, K.J. Alcohol. Clin. Exp. Res. (2000) [Pubmed]
  2. Developmental expression of functional GABAA receptors containing the gamma 2 subunit in neurons derived from embryonal carcinoma (P19) cells. Reynolds, J.N., Prasad, A., Gillespie, L.L., Paterno, G.D. Brain Res. Mol. Brain Res. (1996) [Pubmed]
  3. Blocking chemokine responsive to gamma-2/interferon (IFN)-gamma inducible protein and monokine induced by IFN-gamma activity in vivo reduces the pathogenetic but not the antiviral potential of hepatitis B virus-specific cytotoxic T lymphocytes. Kakimi, K., Lane, T.E., Wieland, S., Asensio, V.C., Campbell, I.L., Chisari, F.V., Guidotti, L.G. J. Exp. Med. (2001) [Pubmed]
  4. Regulation of PPAR gamma gene expression by nutrition and obesity in rodents. Vidal-Puig, A., Jimenez-Liñan, M., Lowell, B.B., Hamann, A., Hu, E., Spiegelman, B., Flier, J.S., Moller, D.E. J. Clin. Invest. (1996) [Pubmed]
  5. Decreased GABAA-receptor clustering results in enhanced anxiety and a bias for threat cues. Crestani, F., Lorez, M., Baer, K., Essrich, C., Benke, D., Laurent, J.P., Belzung, C., Fritschy, J.M., Lüscher, B., Mohler, H. Nat. Neurosci. (1999) [Pubmed]
  6. Structure of human immunoglobulin gamma genes: implications for evolution of a gene family. Takahashi, N., Ueda, S., Obata, M., Nikaido, T., Nakai, S., Honjo, T. Cell (1982) [Pubmed]
  7. Ordering of mouse immunoglobulin heavy chain genes by molecular cloning. Shimizu, A., Takahashi, N., Yamawaki-Kataoka, Y., Nishida, Y., Kataoka, T., Honjo, T. Nature (1981) [Pubmed]
  8. Functional modulation of GABAA receptors by cAMP-dependent protein phosphorylation. Moss, S.J., Smart, T.G., Blackstone, C.D., Huganir, R.L. Science (1992) [Pubmed]
  9. PPARgamma knockdown by engineered transcription factors: exogenous PPARgamma2 but not PPARgamma1 reactivates adipogenesis. Ren, D., Collingwood, T.N., Rebar, E.J., Wolffe, A.P., Camp, H.S. Genes Dev. (2002) [Pubmed]
  10. A functional variant in the peroxisome proliferator-activated receptor gamma2 promoter is associated with predictors of obesity and type 2 diabetes in Pima Indians. Muller, Y.L., Bogardus, C., Beamer, B.A., Shuldiner, A.R., Baier, L.J. Diabetes (2003) [Pubmed]
  11. UL27.5 is a novel gamma2 gene antisense to the herpes simplex virus 1 gene encoding glycoprotein B. Chang, Y.E., Menotti, L., Filatov, F., Campadelli-Fiume, G., Roizman, B. J. Virol. (1998) [Pubmed]
  12. Expression and regulation of glycoprotein C gene of herpes simplex virus 1 resident in a clonal L-cell line. Arsenakis, M., Tomasi, L.F., Speziali, V., Roizman, B., Campadelli-Fiume, G. J. Virol. (1986) [Pubmed]
  13. Characterization of the role of gamma2 R531G mutation in AMP-activated protein kinase in cardiac hypertrophy and Wolff-Parkinson-White syndrome. Davies, J.K., Wells, D.J., Liu, K., Whitrow, H.R., Daniel, T.D., Grignani, R., Lygate, C.A., Schneider, J.E., Noël, G., Watkins, H., Carling, D. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  14. Nova regulates GABA(A) receptor gamma2 alternative splicing via a distal downstream UCAU-rich intronic splicing enhancer. Dredge, B.K., Darnell, R.B. Mol. Cell. Biol. (2003) [Pubmed]
  15. Genetic association of a GABA(A) receptor gamma2 subunit variant with severity of acute physiological dependence on alcohol. Buck, K.J., Hood, H.M. Mamm. Genome (1998) [Pubmed]
  16. GABAA receptor gamma 2 subunit knockdown mice have enhanced anxiety-like behavior but unaltered hypnotic response to benzodiazepines. Chandra, D., Korpi, E.R., Miralles, C.P., De Blas, A.L., Homanics, G.E. BMC neuroscience [electronic resource]. (2005) [Pubmed]
  17. Targeted disruption of the GABA(A) receptor delta subunit gene leads to an up-regulation of gamma 2 subunit-containing receptors in cerebellar granule cells. Tretter, V., Hauer, B., Nusser, Z., Mihalek, R.M., Höger, H., Homanics, G.E., Somogyi, P., Sieghart, W. J. Biol. Chem. (2001) [Pubmed]
  18. Regulation of the expression of GABAA receptor subunits by an antiepileptic drug QYS. Li, X., Yang, Q., Hu, Y. Neurosci. Lett. (2006) [Pubmed]
  19. Uncoupling of GABAA/benzodiazepine receptor alpha 1, beta 2, and gamma 2 subunit mRNA expression in cerebellar Purkinje cells of staggerer mutant mice. Luntz-Leybman, V., Rotter, A., Zdilar, D., Frostholm, A. J. Neurosci. (1995) [Pubmed]
  20. Glucose-Dependent Regulation of {gamma}-Aminobutyric Acid (GABAA) Receptor Expression in Mouse Pancreatic Islet {alpha}-Cells. Bailey, S.J., Ravier, M.A., Rutter, G.A. Diabetes (2007) [Pubmed]
  21. Loss of postsynaptic GABA(A) receptor clustering in gephyrin-deficient mice. Kneussel, M., Brandstätter, J.H., Laube, B., Stahl, S., Müller, U., Betz, H. J. Neurosci. (1999) [Pubmed]
  22. The gamma 2 subunit of GABA(A) receptors is required for maintenance of receptors at mature synapses. Schweizer, C., Balsiger, S., Bluethmann, H., Mansuy, I.M., Fritschy, J.M., Mohler, H., Lüscher, B. Mol. Cell. Neurosci. (2003) [Pubmed]
  23. Differential expression of GABAA/benzodiazepine receptor subunit mRNAs and ligand binding sites in mouse cerebellar neurons following in vivo ethanol administration: an autoradiographic analysis. Wu, C.H., Frostholm, A., De Blas, A.L., Rotter, A. J. Neurochem. (1995) [Pubmed]
  24. Glycine receptors and GABA receptor alpha 1 and gamma 2 subunits during the development of mouse hypoglossal nucleus. Muller, E., Triller, A., Legendre, P. Eur. J. Neurosci. (2004) [Pubmed]
  25. GABARAP is not essential for GABA receptor targeting to the synapse. O'Sullivan, G.A., Kneussel, M., Elazar, Z., Betz, H. Eur. J. Neurosci. (2005) [Pubmed]
  26. Recombinant human IgG1-murine IgE chimeric Ig. Construction, expression, and binding to human Fc gamma receptors. Shopes, B., Weetall, M., Holowka, D., Baird, B. J. Immunol. (1990) [Pubmed]
  27. Constitutive tyrosine phosphorylation of the GABA(A) receptor gamma 2 subunit in rat brain. Brandon, N.J., Delmas, P., Hill, J., Smart, T.G., Moss, S.J. Neuropharmacology (2001) [Pubmed]
  28. Postsynaptic clustering of gamma-aminobutyric acid type A receptors by the gamma3 subunit in vivo. Baer, K., Essrich, C., Benson, J.A., Benke, D., Bluethmann, H., Fritschy, J.M., Lüscher, B. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  29. Leukemia inhibitory factor and its receptor promote adipocyte differentiation via the mitogen-activated protein kinase cascade. Aubert, J., Dessolin, S., Belmonte, N., Li, M., McKenzie, F.R., Staccini, L., Villageois, P., Barhanin, B., Vernallis, A., Smith, A.G., Ailhaud, G., Dani, C. J. Biol. Chem. (1999) [Pubmed]
  30. Netoglitazone is a PPAR-gamma ligand with selective effects on bone and fat. Lazarenko, O.P., Rzonca, S.O., Suva, L.J., Lecka-Czernik, B. Bone (2006) [Pubmed]
  31. The receptor tyrosine kinase MerTK activates phospholipase C gamma2 during recognition of apoptotic thymocytes by murine macrophages. Todt, J.C., Hu, B., Curtis, J.L. J. Leukoc. Biol. (2004) [Pubmed]
  32. Diabetic KKAy mice exhibit increased hepatic PPARgamma1 gene expression and develop hepatic steatosis upon chronic treatment with antidiabetic thiazolidinediones. Bedoucha, M., Atzpodien, E., Boelsterli, U.A. J. Hepatol. (2001) [Pubmed]
  33. Thymosin beta 4 stimulates laminin-5 production independent of TGF-beta. Sosne, G., Xu, L., Prach, L., Mrock, L.K., Kleinman, H.K., Letterio, J.J., Hazlett, L.D., Kurpakus-Wheater, M. Exp. Cell Res. (2004) [Pubmed]
  34. Gephyrin is critical for glycine receptor clustering but not for the formation of functional GABAergic synapses in hippocampal neurons. Lévi, S., Logan, S.M., Tovar, K.R., Craig, A.M. J. Neurosci. (2004) [Pubmed]
  35. The gamma2 subunit of GABA(A) receptors is a substrate for palmitoylation by GODZ. Keller, C.A., Yuan, X., Panzanelli, P., Martin, M.L., Alldred, M., Sassoè-Pognetto, M., Lüscher, B. J. Neurosci. (2004) [Pubmed]
  36. GABAA receptor function and regional analysis of subunit mRNAs in long-sleep and short-sleep mouse brain. Zahniser, N.R., Buck, K.J., Curella, P., McQuilkin, S.J., Wilson-Shaw, D., Miller, C.L., Klein, R.L., Heidenreich, K.A., Keir, W.J., Sikela, J.M. Brain Res. Mol. Brain Res. (1992) [Pubmed]
  37. Regulation of GABAA receptor function by protein kinase C phosphorylation. Krishek, B.J., Xie, X., Blackstone, C., Huganir, R.L., Moss, S.J., Smart, T.G. Neuron (1994) [Pubmed]
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