Genomes and Genes
Gene Symbol: Gabra6
Description: gamma-aminobutyric acid (GABA) A receptor, subunit alpha 6
Alias: GABA-ARalpha6, Gabra-6, alpha6, gamma-aminobutyric acid receptor subunit alpha-6, GABA(A) receptor subunit alpha-6, GABAA receptor alpha 6 subunit, subunit alpha 6 gamma-aminobutyric acid (GABA-A) receptor
- Kaja S, Hann V, Payne H, Thompson C. Aberrant cerebellar granule cell-specific GABAA receptor expression in the epileptic and ataxic mouse mutant, Tottering. Neuroscience. 2007;148:115-25 pubmed..3)H]Muscimol autoradiography identified that this was partly due to a significant loss of CGC-specific alpha6 subunit-containing GABA(A) receptor subtypes...
- Sampson M, Lovell R, Craigen W. Isolation, characterization, and mapping of two mouse mitochondrial voltage-dependent anion channel isoforms. Genomics. 1996;33:283-8 pubmed..The mouse VDAC5 gene was mapped using an interspecies DNA mapping panel to the proximal region of chromosome 11, and the mouse VDAC6 gene was mapped using a panel to the proximal region of chromosome 14. ..
- Oki T, Yamazaki K, Kuromitsu J, Okada M, Tanaka I. cDNA cloning and mapping of a novel subtype of glutamine:fructose-6-phosphate amidotransferase (GFAT2) in human and mouse. Genomics. 1999;57:227-34 pubmed..GFAT2 can provide insights into understanding the roles of the hexosamine pathway in various tissues, particularly with the development of glucose toxicity and diabetes complications. ..
- Wu C, Frostholm A, De Blas A, Rotter A. Differential expression of GABAA/benzodiazepine receptor subunit mRNAs and ligand binding sites in mouse cerebellar neurons following in vivo ethanol administration: an autoradiographic analysis. J Neurochem. 1995;65:1229-39 pubmed..The observed changes were not restricted to any one cerebellar cell type, because subunit expression in Purkinje, granule, and deep cerebellar cells was similarly affected. ..
- Homanics G, Ferguson C, Quinlan J, Daggett J, Snyder K, Lagenaur C, et al. Gene knockout of the alpha6 subunit of the gamma-aminobutyric acid type A receptor: lack of effect on responses to ethanol, pentobarbital, and general anesthetics. Mol Pharmacol. 1997;51:588-96 pubmedThe alpha6 subunit of the gamma-aminobutyric acid type A receptor (GABA(A)-R) has been implicated in mediating the intoxicating effects of ethanol and the motor ataxic effects of general anesthetics...
- Bouslama Oueghlani L, Wehrle R, Sotelo C, Dusart I. The developmental loss of the ability of Purkinje cells to regenerate their axons occurs in the absence of myelin: an in vitro model to prevent myelination. J Neurosci. 2003;23:8318-29 pubmed..Thus, the Purkinje cell developmental switch from axonal regeneration to lack of regeneration does not appear to be regulated by myelin. ..
- Tretter V, Hauer B, Nusser Z, Mihalek R, Hoger H, Homanics G, et al. 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. J Biol Chem. 2001;276:10532-8 pubmed..The availability of the delta subunit, thus, influences the level of expression or the extent of assembly of the gamma(2) subunit, although these two subunits do not occur in the same receptor. ..
- Spicer A, Roller M, Camper S, McPherson J, Wasmuth J, Hakim S, et al. The human and mouse receptors for hyaluronan-mediated motility, RHAMM, genes (HMMR) map to human chromosome 5q33.2-qter and mouse chromosome 11. Genomics. 1995;30:115-7 pubmed..The RHAMM gene location and its ability to transform cells when overexpressed implicate RHAMM as a possible candidate gene in the pathogenesis of the recently described t(5;14)(q33-q34;q11) acute lymphoblastic leukemias. ..
- Wright K, Lyon K, Leung H, Leahy D, Ma L, Ginty D. Dystroglycan organizes axon guidance cue localization and axonal pathfinding. Neuron. 2012;76:931-44 pubmed publisher..These findings establish a novel role for glycosylated dystroglycan as a key determinant of axon guidance cue distribution and function in the mammalian nervous system. ..
- Kato K. Novel GABAA receptor alpha subunit is expressed only in cerebellar granule cells. J Mol Biol. 1990;214:619-24 pubmed..This is the first demonstration of the exclusive presence of a neuroreceptor subtype in a single neuronal cell type. ..
- Varecka L, Wu C, Rotter A, Frostholm A. GABAA/benzodiazepine receptor alpha 6 subunit mRNA in granule cells of the cerebellar cortex and cochlear nuclei: expression in developing and mutant mice. J Comp Neurol. 1994;339:341-52 pubmed..The intensity of the hybridization signal in both regions increased rapidly until postnatal day 14, after which it increased more gradually, reaching adult levels during postnatal week 3.(ABSTRACT TRUNCATED AT 250 WORDS) ..
- Koirala S, Jin Z, Piao X, Corfas G. GPR56-regulated granule cell adhesion is essential for rostral cerebellar development. J Neurosci. 2009;29:7439-49 pubmed publisher..These studies establish a novel role for GPR56 in the adhesion of developing neurons to basal lamina molecules and suggest that this adhesion is critical for maintenance of the pia and proper cerebellar morphogenesis. ..
- Gill K, Boyle A. Genetic basis for the psychostimulant effects of nicotine: a quantitative trait locus analysis in AcB/BcA recombinant congenic mice. Genes Brain Behav. 2005;4:401-11 pubmed..A number of putative candidate genes were in proximity to regions identified with nicotine sensitivity, including the alpha2 subunit of the nicotinic acetylcholine receptor and the dopamine D3 receptor...
- Sinkkonen S, Vekovischeva O, Möykkynen T, Ogris W, Sieghart W, Wisden W, et al. Behavioural correlates of an altered balance between synaptic and extrasynaptic GABAAergic inhibition in a mouse model. Eur J Neurosci. 2004;20:2168-78 pubmed..Thy1alpha6 mice with ectopic forebrain expression of GABAA receptor alpha6 subunits exhibit increased extrasynaptic GABAA receptor-mediated background conductance and reduced synaptic GABAA ..
- Seja P, Schonewille M, Spitzmaul G, Badura A, Klein I, Rudhard Y, et al. Raising cytosolic Cl- in cerebellar granule cells affects their excitability and vestibulo-ocular learning. EMBO J. 2012;31:1217-30 pubmed publisher..These functions, however, were affected by disruption of Kcc2 in PCs. GC excitability plays a previously unknown, but specific role in consolidation of phase learning. ..
- Lin X, Shah S, Bulleit R. The expression of MEF2 genes is implicated in CNS neuronal differentiation. Brain Res Mol Brain Res. 1996;42:307-16 pubmed..This time course of expression coincides with the expression of GABA(A) receptor alpha6 subunit RNA, a marker for the differentiation of the mature cerebellar granule neurons...
- Korpi E, Kleingoor C, Kettenmann H, Seeburg P. Benzodiazepine-induced motor impairment linked to point mutation in cerebellar GABAA receptor. Nature. 1993;361:356-9 pubmed..Our results suggest that cerebellar motor control may be a distinct behavioural correlate of the alpha 6-subunit-containing GABAA receptor subtype. ..
- Jessop D. Review: Central non-glucocorticoid inhibitors of the hypothalamo-pituitary-adrenal axis. J Endocrinol. 1999;160:169-80 pubmed
- McAndrew P, Frostholm A, Evans J, Zdilar D, Goldowitz D, Chiu I, et al. Novel receptor protein tyrosine phosphatase (RPTPrho) and acidic fibroblast growth factor (FGF-1) transcripts delineate a rostrocaudal boundary in the granule cell layer of the murine cerebellar cortex. J Comp Neurol. 1998;391:444-55 pubmed..The restricted pattern of FGF-1 and RPTPrho implies that these molecules may have specific signaling roles in the tyrosine phosphorylation/dephosphorylation pathway in the anterior compartment of the adult cerebellar cortex. ..
- Jones A, Bahn S, Grant A, Kohler M, Wisden W. Characterization of a cerebellar granule cell-specific gene encoding the gamma-aminobutyric acid type A receptor alpha 6 subunit. J Neurochem. 1996;67:907-16 pubmed..Thus, we have defined a region containing the basal promoter of the alpha 6 subunit gene and that confers neuron-specific expression. ..
- Zindy F, Kawauchi D, Lee Y, Ayrault O, Ben Merzoug L, McKinnon P, et al. Role of the miR-17?92 cluster family in cerebellar and medulloblastoma development. Biol Open. 2014;3:597-605 pubmed publisher..Taken together, our findings demonstrate that the miR-17?92 cluster is dispensable for cerebellar development, but required for SHH-MB development. ..
- Kumar M, Tyagi N, Moshal K, Sen U, Pushpakumar S, Vacek T, et al. GABAA receptor agonist mitigates homocysteine-induced cerebrovascular remodeling in knockout mice. Brain Res. 2008;1221:147-53 pubmed publisher..The results suggested that Hcy caused cerebral interstitial remodeling in brain by distorting the extracellular matrix, thus increasing the blood brain permeability; treatment with muscimol mitigated BBB permeability. ..
- Clopath C, Badura A, De Zeeuw C, Brunel N. A cerebellar learning model of vestibulo-ocular reflex adaptation in wild-type and mutant mice. J Neurosci. 2014;34:7203-15 pubmed publisher..The detailed model reproduces both the behavioral and electrophysiological data of both the wild-type and mutant mice and allows for experimentally testable predictions. ..
- Heglind M, Cederberg A, Aquino J, Lucas G, Ernfors P, Enerback S. Lack of the central nervous system- and neural crest-expressed forkhead gene Foxs1 affects motor function and body weight. Mol Cell Biol. 2005;25:5616-25 pubmed..This points toward a role for Foxs1 in the integration and processing of neuronal signals of importance for energy turnover and motor function. ..
- Takahashi N, Ko M. The short 3'-end region of complementary DNAs as PCR-based polymorphic markers for an expression map of the mouse genome. Genomics. 1993;16:161-8 pubmed
- Ives J, Drewery D, Thompson C. Differential cell surface expression of GABAA receptor alpha1, alpha6, beta2 and beta3 subunits in cultured mouse cerebellar granule cells influence of cAMP-activated signalling. J Neurochem. 2002;80:317-27 pubmed..Initially the steady-state distribution of GABAR alpha1, alpha6, beta2 and beta3 subunits between the cell surface and cell interior was quantified...
- Korpi E, Koikkalainen P, Vekovischeva O, Mäkelä R, Kleinz R, Uusi Oukari M, et al. Cerebellar granule-cell-specific GABAA receptors attenuate benzodiazepine-induced ataxia: evidence from alpha 6-subunit-deficient mice. Eur J Neurosci. 1999;11:233-40 pubmed..We conclude that GABAA receptor alpha 6 subunit-dependent actions in the cerebellar cortex can be compensated by other receptor subtypes; but if not ..
- Lancaster M, Gopal D, Kim J, Saleem S, Silhavy J, Louie C, et al. Defective Wnt-dependent cerebellar midline fusion in a mouse model of Joubert syndrome. Nat Med. 2011;17:726-31 pubmed publisher..Our findings implicate a defect in Wnt signaling in the cerebellar midline phenotype seen in Joubert syndrome that can be overcome with Wnt stimulation...
- Bertoni C, Appolloni M, Stirling J, Li S, Li Y, Orlacchio A, et al. Structural organization and expression of the gene for the mouse GM2 activator protein. Mamm Genome. 1997;8:90-3 pubmed..Northern blot analysis demonstrated variation in the GM2 activator protein mRNA expression during mouse development. Gm2a was mapped to Chromosome (Chr) 11, where it co-segregated with Csfgm. ..
- Birkenmeier E, Rowe L, Crossman M, Gordon J. Ileal lipid-binding protein (Illbp) gene maps to mouse chromosome 11. Mamm Genome. 1994;5:805-6 pubmed
- Mizokami A, Tanaka H, Ishibashi H, Umebayashi H, Fukami K, Takenawa T, et al. GABA(A) receptor subunit alteration-dependent diazepam insensitivity in the cerebellum of phospholipase C-related inactive protein knockout mice. J Neurochem. 2010;114:302-10 pubmed publisher..assemble with any form of beta and the gamma2 subunits to produce diazepam-sensitive receptors, whereas alpha4 or alpha6/beta/gamma2 receptors are diazepam-insensitive...
- Weiss R, Kostrub C, Enoch T, Leder P. Mouse Hus1, a homolog of the Schizosaccharomyces pombe hus1+ cell cycle checkpoint gene. Genomics. 1999;59:32-9 pubmed..Finally, mouse Hus1 was found to be expressed in a variety of adult tissues and at several stages of embryonic development. ..
- Uusi Oukari M, Heikkila J, Sinkkonen S, Mäkelä R, Hauer B, Homanics G, et al. Long-range interactions in neuronal gene expression: evidence from gene targeting in the GABA(A) receptor beta2-alpha6-alpha1-gamma2 subunit gene cluster. Mol Cell Neurosci. 2000;16:34-41 pubmedClustering of GABA(A) receptor alpha1, alpha6, beta2, and gamma2 subunit genes on mouse chromosome 11/human chromosome 5 may have functional significance for coordinating expression patterns, but until now there has been no evidence for ..
- Klingensmith J, Yang Y, Axelrod J, Beier D, Perrimon N, Sussman D. Conservation of dishevelled structure and function between flies and mice: isolation and characterization of Dvl2. Mech Dev. 1996;58:15-26 pubmed..Thus, Dvl2 encodes a mammalian homolog of dsh which can transduce the Wingless signal. ..
- Jones A, Korpi E, McKernan R, Pelz R, Nusser Z, Mäkelä R, et al. Ligand-gated ion channel subunit partnerships: GABAA receptor alpha6 subunit gene inactivation inhibits delta subunit expression. J Neurosci. 1997;17:1350-62 pubmedCerebellar granule cells express six GABAA receptor subunits abundantly (alpha1, alpha6, beta2, beta3, gamma2, and delta) and assemble various pentameric receptor subtypes with unknown subunit compositions; however, the rules guiding ..
- Chen H, McCaffery J, Chan D. Mitochondrial fusion protects against neurodegeneration in the cerebellum. Cell. 2007;130:548-62 pubmed
- Friedel R, Kerjan G, Rayburn H, Schüller U, Sotelo C, Tessier Lavigne M, et al. Plexin-B2 controls the development of cerebellar granule cells. J Neurosci. 2007;27:3921-32 pubmed..Many differentiated granule cells migrate inside the cerebellum and keep proliferating. These results reveal that Plexin-B2 controls the balance between proliferation and differentiation in granule cells. ..
- Levin S, Khaliq Z, Aman T, Grieco T, Kearney J, Raman I, et al. Impaired motor function in mice with cell-specific knockout of sodium channel Scn8a (NaV1.6) in cerebellar purkinje neurons and granule cells. J Neurophysiol. 2006;96:785-93 pubmed..The loss of these channels leads to a decrease in Purkinje cell firing rates as well as a modification of the synaptic properties of afferent parallel fibers, with the ultimate consequence of disrupting motor behavior. ..
- Hood H, Metten P, Crabbe J, Buck K. Fine mapping of a sedative-hypnotic drug withdrawal locus on mouse chromosome 11. Genes Brain Behav. 2006;5:1-10 pubmed
- Wang W, Stock R, Gronostajski R, Wong Y, Schachner M, Kilpatrick D. A role for nuclear factor I in the intrinsic control of cerebellar granule neuron gene expression. J Biol Chem. 2004;279:53491-7 pubmed..The alpha6 subunit of the gamma-aminobutyric acid type A (GABA(A)) receptor (GABRA6) is preferentially expressed in ..
- Mellor J, Merlo D, Jones A, Wisden W, Randall A. Mouse cerebellar granule cell differentiation: electrical activity regulates the GABAA receptor alpha 6 subunit gene. J Neurosci. 1998;18:2822-33 pubmedGABAA receptor alpha6 subunit gene expression marks cerebellar granule cell maturation. To study this process, we used the Deltaalpha6lacZ mouse line, which has a lacZ reporter inserted into the alpha6 gene...
- 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. ..
- Bahn S, Harvey R, Darlison M, Wisden W. Conservation of gamma-aminobutyric acid type A receptor alpha 6 subunit gene expression in cerebellar granule cells. J Neurochem. 1996;66:1810-8 pubmed..g., granule cell-specific enhancers, have also been conserved. ..
- Brickley S, Revilla V, Cull Candy S, Wisden W, Farrant M. Adaptive regulation of neuronal excitability by a voltage-independent potassium conductance. Nature. 2001;409:88-92 pubmed..Here we show that this tonic conductance is absent in granule cells that lack the alpha6 and delta-subunits of the GABAA receptor...
- Leggio G, Torrisi S, Castorina A, Platania C, Impellizzeri A, Fidilio A, et al. Dopamine D3 receptor-dependent changes in alpha6 GABAA subunit expression in striatum modulate anxiety-like behaviour: Responsiveness and tolerance to diazepam. Eur Neuropsychopharmacol. 2015;25:1427-36 pubmed publisher..Modulation of GABAA receptor by DA transmission may be involved in the mechanisms of anxiety and, if occurring in humans, may have therapeutic relevance following repeated use of drugs targeting D3R. ..
- Zahniser N, Buck K, Curella P, McQuilkin S, Wilson Shaw D, Miller C, et al. GABAA receptor function and regional analysis of subunit mRNAs in long-sleep and short-sleep mouse brain. Brain Res Mol Brain Res. 1992;14:196-206 pubmed
- 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. ..
- 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..Given the reciprocal relationship of alpha2 and alpha6 expression, we hypothesised that there is a developmental switch in the expression of these subunits in GnRH-1 ..
- 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. ..
- Kontturi L, Aalto A, Wallner M, Uusi Oukari M. The cerebellar GABAAR ?6-R100Q polymorphism alters ligand binding in outbred Sprague-Dawley rats in a similar manner as in selectively bred AT and ANT rats. Alcohol. 2011;45:653-61 pubmed publisher..The results indicate that in addition to the central role of the homologous ?6-100R/Q (?1-101H) residue in BZ binding and efficacy, this critical BZ binding site residue has a major impact on BZ binding kinetics. ..
- Mo J, Kim C, Lee D, Sun W, Lee H, Kim H. Early growth response 1 (Egr-1) directly regulates GABAA receptor Î±2, Î±4, and Î¸ subunits in the hippocampus. J Neurochem. 2015;133:489-500 pubmed publisher..Neuronal activity-dependent up-regulation of Egr-1 might lead to altered subtypes of GABAA receptors for the maintenance of homeostatic excitatory and inhibitory balance for the regulation of synaptic strength. ..
- 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..phenotype of seven mouse lines with targeted deletion of a GABA(A) receptor subunit (alpha1, alpha2, alpha5, alpha6, beta2, beta3, or delta)...
- Bahn S, Jones A, Wisden W. Directing gene expression to cerebellar granule cells using gamma-aminobutyric acid type A receptor alpha6 subunit transgenes. Proc Natl Acad Sci U S A. 1997;94:9417-21 pubmedExpression of the gamma-aminobutyric acid type A receptor alpha6 subunit gene is restricted to differentiated granule cells of the cerebellum and cochlear nucleus. The mechanisms underlying this limited expression are unknown...
- Takayama C, Inoue Y. Morphological development and maturation of the GABAergic synapses in the mouse cerebellar granular layer. Brain Res Dev Brain Res. 2004;150:177-90 pubmed..In situ hybridization and immunohistochemistry for the GABA(A) receptor alpha1 and alpha6 subunits, which are mainly involved in inhibitory synaptic transmission, demonstrated that both subunits appeared ..
- Nusser Z, Ahmad Z, Tretter V, Fuchs K, Wisden W, Sieghart W, et al. Alterations in the expression of GABAA receptor subunits in cerebellar granule cells after the disruption of the alpha6 subunit gene. Eur J Neurosci. 1999;11:1685-97 pubmed..We used the targeted disruption of the alpha6 subunit gene to test for changes in the expression of other GABAA receptor subunits...
- Blaess S, Graus Porta D, Belvindrah R, Radakovits R, Pons S, Littlewood Evans A, et al. Beta1-integrins are critical for cerebellar granule cell precursor proliferation. J Neurosci. 2004;24:3402-12 pubmed
- Metzger M, Walser S, Aprile Garcia F, Dedic N, Chen A, Holsboer F, et al. Genetically dissecting P2rx7 expression within the central nervous system using conditional humanized mice. Purinergic Signal. 2017;13:153-170 pubmed publisher..In addition, this conditional allele will enable future loss-of-function studies in conjunction with mouse models for CNS disorders. ..
- Martenson J, Yamasaki T, Chaudhury N, Albrecht D, Tomita S. Assembly rules for GABAA receptor complexes in the brain. elife. 2017;6: pubmed publisher..These findings establish the first molecular model for combinatorial GABAAR assembly in vivo and reveal an assembly pathway regulating GABAAR synaptic localization. ..
- Zhou H, Lin Z, Voges K, Ju C, Gao Z, Bosman L, et al. Cerebellar modules operate at different frequencies. elife. 2014;3:e02536 pubmed publisher..DOI: http://dx.doi.org/10.7554/eLife.02536.001. ..
- Yoshikawa T, Watanabe A, Ishitsuka Y, Nakaya A, Nakatani N. Identification of multiple genetic loci linked to the propensity for "behavioral despair" in mice. Genome Res. 2002;12:357-66 pubmed..The present quantitative trait study should open up avenues for identifying novel molecular targets for antidepressants and unraveling the complex genetic mechanisms of depressive and anxiety disorders. ..
- Burrows H, Seasholtz A, Camper S. Localization of the corticotropin-releasing hormone receptor gene on mouse chromosome 11. Mamm Genome. 1995;6:55-6 pubmed