Genomes and Genes
Gene Symbol: Gabra5
Description: gamma-aminobutyric acid (GABA) A receptor, subunit alpha 5
Alias: A230018I05Rik, gamma-aminobutyric acid receptor subunit alpha-5, GABA(A) receptor subunit alpha-5, ligand-gated ion channel subunit
- Khrestchatisky M, MacLennan A, Chiang M, Xu W, Jackson M, Brecha N, et al. A novel alpha subunit in rat brain GABAA receptors. Neuron. 1989;3:745-53 pubmed..Picrotoxin alone, applied to oocytes producing the alpha and beta polypeptides, elicited an outward current. We suggest that these polypeptides together produce GABA-gated ion channels that can also open spontaneously. ..
- Zurek A, Yu J, Wang D, Haffey S, Bridgwater E, Penna A, et al. Sustained increase in Î±5GABAA receptor function impairs memory after anesthesia. J Clin Invest. 2014;124:5437-41 pubmed publisher..Thus, Î±5GABA(A)R function does not return to baseline after the anesthetic is eliminated, suggesting a mechanism to account for persistent memory deficits after general anesthesia. ..
- Nakatsu Y, Tyndale R, DeLorey T, Durham Pierre D, Gardner J, McDanel H, et al. A cluster of three GABAA receptor subunit genes is deleted in a neurological mutant of the mouse p locus. Nature. 1993;364:448-50 pubmed..The human homologue of the region deleted in p(cp) mice is associated with Angelman syndrome. Thus, p(cp) mice may be useful in defining the region containing the gene(s) for this syndrome. ..
- Tan S, Rudd J, Yew D. Gene expression changes in GABA(A) receptors and cognition following chronic ketamine administration in mice. PLoS ONE. 2011;6:e21328 pubmed publisher..In particular, there was a significant up-regulation of both mRNA and protein levels of the alpha 5 subunit (Gabra5) of the GABA(A) receptors in the prefrontal cortex...
- 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. ..
- Ghafari M, Falsafi S, Szodorai E, Kim E, Li L, Hoger H, et al. Formation of GABAA receptor complexes containing ?1 and ?5 subunits is paralleling a multiple T-maze learning task in mice. Brain Struct Funct. 2017;222:549-561 pubmed publisher..Taken together, these results suggest that ?1, ?5 and ?2-containing hippocampal GABAAR complexes play an essential role in spatial learning and memory in which targeted disruption of the ?1 subunit produces profound deficits. ..
- Knoll J, Sinnett D, Wagstaff J, Glatt K, Wilcox A, Whiting P, et al. FISH ordering of reference markers and of the gene for the alpha 5 subunit of the gamma-aminobutyric acid receptor (GABRA5) within the Angelman and Prader-Willi syndrome chromosomal regions. Hum Mol Genet. 1993;2:183-9 pubmed..Our results provide a framework map of chromosome 15q11-q13 into which additional markers can be oriented and allow a further differentiation of the critical genetic regions of the two syndromes. ..
- Jessop D. Review: Central non-glucocorticoid inhibitors of the hypothalamo-pituitary-adrenal axis. J Endocrinol. 1999;160:169-80 pubmed
- Culiat C, Stubbs L, Nicholls R, Montgomery C, Russell L, Johnson D, et al. 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. Proc Natl Acad Sci U S A. 1993;90:5105-9 pubmed..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...
- Balic E, Rudolph U, Fritschy J, Mohler H, Benke D. The alpha5(H105R) mutation impairs alpha5 selective binding properties by altered positioning of the alpha5 subunit in GABAA receptors containing two distinct types of alpha subunits. J Neurochem. 2009;110:244-54 pubmed publisher..These findings imply an important role of histidine 105 in determining the position of the alpha5 subunit within the receptor complex by determining the affinity for assembly with the gamma2 subunit. ..
- Dhar M, Hauser L, Nicholls R, Johnson D. Physical mapping of the pink-eyed dilution complex in mouse chromosome 7 shows that Atp10c is the only transcript between Gabrb3 and Ube3a. DNA Seq. 2004;15:306-9 pubmed..Data show that Atp10c, a novel type IV ATPase a putative phospholipid transporter, is the only coding unit in this region of the chromosome. ..
- Gerdjikov T, Rudolph U, Keist R, Mohler H, Feldon J, Yee B. Hippocampal alpha 5 subunit-containing GABA A receptors are involved in the development of the latent inhibition effect. Neurobiol Learn Mem. 2008;89:87-94 pubmed..This observed phenotype suggests that specific activation of these extrasynaptic GABA(A) receptors may confer therapeutic potential against the failure to show selectivity in learning by human psychotic patients. ..
- Martin L, Zurek A, Bonin R, Oh G, Kim J, Mount H, et al. The sedative but not the memory-blocking properties of ethanol are modulated by ?5-subunit-containing ?-aminobutyric acid type A receptors. Behav Brain Res. 2011;217:379-85 pubmed publisher..Null mutant mice lacking the ?5 subunit (Gabra5-/-) and wild-type mice were equally impaired in contextual fear conditioning by moderate (1mg/kg) and high (1...
- 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. ..
- Yee B, Hauser J, Dolgov V, Keist R, Mohler H, Rudolph U, et al. GABA receptors containing the alpha5 subunit mediate the trace effect in aversive and appetitive conditioning and extinction of conditioned fear. Eur J Neurosci. 2004;20:1928-36 pubmed..Our results identify neuronal inhibition in the hippocampus mediated via alpha5 GABAA receptors as a critical control element in the regulation of the acquisition and expression of associative memory. ..
- Brilliant M, Ching A, Nakatsu Y, Eicher E. The original pink-eyed dilution mutation (p) arose in Asiatic mice: implications for the H4 minor histocompatibility antigen, Myod1 regulation and the origin of inbred strains. Genetics. 1994;138:203-11 pubmed..DNA (about 5 cM), including the loci Myod1, p, three clustered GABAA receptor subunit loci (Gabrg3, Gabra5 and Gabrb3), and Snrpn...
- Culiat C, Stubbs L, Montgomery C, Russell L, Rinchik E. Phenotypic consequences of deletion of the gamma 3, alpha 5, or beta 3 subunit of the type A gamma-aminobutyric acid receptor in mice. Proc Natl Acad Sci U S A. 1994;91:2815-8 pubmedThree genes (Gabrg3, Gabra5, and Gabrb3) encoding the gamma 3, alpha 5, and beta 3 subunits of the type A gamma-aminobutyric acid receptor, respectively, are known to map near the pink-eyed dilution (p) locus in mouse chromosome 7...
- 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
- Glykys J, Mody I. The main source of ambient GABA responsible for tonic inhibition in the mouse hippocampus. J Physiol. 2007;582:1163-78 pubmed..Our results are consistent with most of hippocampal tonic inhibitory current being mediated by GABA released from the very vesicles responsible for activating phasic inhibition. ..
- Dhar M, Johnson D. A microsatellite map of the pink-eyed dilution (p) deletion complex in mouse chromosome 7. Mamm Genome. 1997;8:143-5 pubmed
- Perez Sanchez J, Lorenzo L, Lecker I, Zurek A, Labrakakis C, Bridgwater E, et al. ?5GABAA Receptors Mediate Tonic Inhibition in the Spinal Cord Dorsal Horn and Contribute to the Resolution Of Hyperalgesia. J Neurosci Res. 2017;95:1307-1318 pubmed publisher..and behavioral approaches in male, null-mutant mice lacking the GABAA R ?5 subunit (Gabra5-/-) and wild-type mice (WT)...
- Stephens D, Pistovcakova J, Worthing L, Atack J, Dawson G. Role of GABAA alpha5-containing receptors in ethanol reward: the effects of targeted gene deletion, and a selective inverse agonist. Eur J Pharmacol. 2005;526:240-50 pubmed..Although inverse agonists acting at alpha5-containing receptors reduce ethanol self-administration, alpha5 subunits may not be essential to signaling ethanol reward. ..
- Penna A, Wang D, Yu J, Lecker I, Brown P, Bowie D, et al. Hydrogen peroxide increases GABAA receptor-mediated tonic current in hippocampal neurons. J Neurosci. 2014;34:10624-34 pubmed publisher..These results suggest that GABAA receptor-mediated tonic current, which is potentiated by H2O2, might contribute to H2O2-induced brain dysfunction. ..
- Clarkson A, Huang B, Macisaac S, Mody I, Carmichael S. Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke. Nature. 2010;468:305-9 pubmed publisher..Together, our results identify new pharmacological targets and provide the rationale for a novel strategy to promote recovery after stroke and possibly other brain injuries. ..
- Mesbah Oskui L, Penna A, Orser B, Horner R. Reduced expression of Î±5GABAA receptors elicits autism-like alterations in EEG patterns and sleep-wake behavior. Neurotoxicol Teratol. 2017;61:115-122 pubmed publisher..Genetically modified mice that lack Î±5GABAARs (Gabra5-/-) exhibit autism-like behaviors and both enhanced and impaired learning and memory, depending on the ..
- Gustincich S, Feigenspan A, Sieghart W, Raviola E. Composition of the GABA(A) receptors of retinal dopaminergic neurons. J Neurosci. 1999;19:7812-22 pubmed..Therefore, DA cells possess at least two types of GABA(A) receptors localized in different synapses. Furthermore, they exhibit multiple extrasynaptic GABA(A) receptors. ..
- Dellovade T, Davis A, Ferguson C, Sieghart W, Homanics G, Tobet S. GABA influences the development of the ventromedial nucleus of the hypothalamus. J Neurobiol. 2001;49:264-76 pubmed..These data suggest that GABA is important for the organization of cells during VMH formation. ..
- Crestani F, Keist R, Fritschy J, Benke D, Vogt K, Prut L, et al. Trace fear conditioning involves hippocampal alpha5 GABA(A) receptors. Proc Natl Acad Sci U S A. 2002;99:8980-5 pubmed..Thus, the largely extrasynaptic alpha5GABA(A) receptors in hippocampal pyramidal cells are implicated as control elements of the temporal association of threat cues in trace fear conditioning. ..
- Caraiscos V, Newell J, You Ten K, Elliott E, Rosahl T, Wafford K, et al. Selective enhancement of tonic GABAergic inhibition in murine hippocampal neurons by low concentrations of the volatile anesthetic isoflurane. J Neurosci. 2004;24:8454-8 pubmed..These studies suggest that an increased tonic inhibition in the hippocampus may contribute to amnestic properties of volatile anesthetics. ..
- Towers S, Gloveli T, Traub R, Driver J, Engel D, Fradley R, et al. Alpha 5 subunit-containing GABAA receptors affect the dynamic range of mouse hippocampal kainate-induced gamma frequency oscillations in vitro. J Physiol. 2004;559:721-8 pubmed..The data suggest that loss of this GABAA receptor subunit alters the dynamic profile of gamma oscillations to changes in network drive, possibly via actions of GABA at extrasynaptic receptors. ..
- Hauser J, Rudolph U, Keist R, Mohler H, Feldon J, Yee B. Hippocampal alpha5 subunit-containing GABAA receptors modulate the expression of prepulse inhibition. Mol Psychiatry. 2005;10:201-7 pubmed
- van Rijnsoever C, Täuber M, Choulli M, Keist R, Rudolph U, Mohler H, et al. Requirement of alpha5-GABAA receptors for the development of tolerance to the sedative action of diazepam in mice. J Neurosci. 2004;24:6785-90 pubmed..Thus, the chronic activation of alpha(5)-GABA(A) receptors is crucial for the normal development of sedative tolerance to diazepam, which manifests itself in conjunction with alpha1-GABA(A) receptors. ..
- Deprez F, Vogt F, Floriou Servou A, Lafourcade C, Rudolph U, Tyagarajan S, et al. Partial inactivation of GABAA receptors containing the Î±5 subunit affects the development of adult-born dentate gyrus granule cells. Eur J Neurosci. 2016;44:2258-71 pubmed publisher..b>Gabra5-null mice and Î±5 subunit((H105R)) knock-in mice exhibit signs of hippocampal dysfunction, but are capable of ..
- 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. ..
- Wang D, Zurek A, Lecker I, Yu J, Abramian A, Avramescu S, et al. Memory deficits induced by inflammation are regulated by ?5-subunit-containing GABAA receptors. Cell Rep. 2012;2:488-96 pubmed publisher..Collectively, these results show that ?5GABA(A) receptor activity increases during inflammation and that this increase is critical for inflammation-induced memory deficits. ..
- Cheng V, Martin L, Elliott E, Kim J, Mount H, Taverna F, et al. Alpha5GABAA receptors mediate the amnestic but not sedative-hypnotic effects of the general anesthetic etomidate. J Neurosci. 2006;26:3713-20 pubmed..Thus, the amnestic and sedative-hypnotic properties of etomidate can be dissociated on the basis of GABAAR subtype pharmacology. ..
- 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. ..
- Behlke L, Foster R, Liu J, Benke D, Benham R, Nathanson A, et al. A Pharmacogenetic 'Restriction-of-Function' Approach Reveals Evidence for Anxiolytic-Like Actions Mediated by ?5-Containing GABAA Receptors in Mice. Neuropsychopharmacology. 2016;41:2492-501 pubmed publisher..Thus, ?5-GABAARs may be suitable targets for novel anxiolytic drugs. ..
- Engin E, Zarnowska E, Benke D, Tsvetkov E, Sigal M, Keist R, et al. Tonic Inhibitory Control of Dentate Gyrus Granule Cells by Î±5-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. ..
- Greger V, Knoll J, Woolf E, Glatt K, Tyndale R, DeLorey T, et al. The gamma-aminobutyric acid receptor gamma 3 subunit gene (GABRG3) is tightly linked to the alpha 5 subunit gene (GABRA5) on human chromosome 15q11-q13 and is transcribed in the same orientation. Genomics. 1995;26:258-64 pubmed..One such cluster, which consists of the GABAA receptor beta 3 (GABRB3) and alpha 5 (GABRA5) subunit genes, is located in chromosome 15q11-q13...
- Sinnett D, Wagstaff J, Glatt K, Woolf E, Kirkness E, Lalande M. High-resolution mapping of the gamma-aminobutyric acid receptor subunit beta 3 and alpha 5 gene cluster on chromosome 15q11-q13, and localization of breakpoints in two Angelman syndrome patients. Am J Hum Genet. 1993;52:1216-29 pubmed..to determine the genomic organization of the GABAA receptor beta 3 subunit gene (GABRB3) and alpha 5 subunit gene (GABRA5) in chromosome 15q11-q13, we have constructed a high-resolution physical map using the combined techniques of ..
- Fritschy J, Benke D, Johnson D, Mohler H, Rudolph U. GABAA-receptor alpha-subunit is an essential prerequisite for receptor formation in vivo. Neuroscience. 1997;81:1043-53 pubmed..Thus, the alpha-subunit, unlike the gamma 2-subunit, might play a major role in the assembly or targeting of GABAA-receptor complexes. ..
- Hausrat T, Muhia M, Gerrow K, Thomas P, Hirdes W, Tsukita S, et al. Radixin regulates synaptic GABAA receptor density and is essential for reversal learning and short-term memory. Nat Commun. 2015;6:6872 pubmed publisher..Our data suggest an additional mode of synaptic plasticity, in which extrasynaptic receptor reservoirs supply synaptic GABAARs. ..
- Ling I, Mihalik B, Etherington L, Kapus G, PÃ¡lvÃ¶lgyi A, Gigler G, et al. A novel GABA(A) alpha 5 receptor inhibitor with therapeutic potential. Eur J Pharmacol. 2015;764:497-507 pubmed publisher..In summary, we have discovered a first-in-class GABA-site inhibitor of extra-synaptic GABAA Î±5 receptors that has promising drug-like properties and warrants further development. ..
- Glatt K, Sinnett D, Lalande M. Dinucleotide repeat polymorphism at the GABAA receptor alpha 5 (GABRA5) locus at chromosome 15q11-q13. Hum Mol Genet. 1992;1:348 pubmed
- Andäng M, Hjerling Leffler J, Moliner A, Lundgren T, Castelo Branco G, Nanou E, et al. Histone H2AX-dependent GABA(A) receptor regulation of stem cell proliferation. Nature. 2008;451:460-4 pubmed publisher..These results indicate the presence of a fundamentally different mechanism of proliferation control in these stem cells, in comparison with most somatic cells, involving proteins in the DNA damage checkpoint pathway. ..
- Liu Z, Kamatchi G, Moreira T, Mu W, Burt D. The alpha5 subunit of the murine type A GABA receptor. Brain Res Mol Brain Res. 1998;59:84-9 pubmed..Finally, we present preliminary evidence for rare alternative splicing of this subunit's message, in the N-terminal extracellular domain, to give a form not translatable into a functional protein. ..
- Megumi T, Song C, Park Y, Tanaka Y, Uchida I, Okumoto M. Mapping of putative ether-anesthesia resistance gene using C57BL/6J and MSM/Ms mouse strains. J Anesth. 2004;18:267-76 pubmed..Our findings should be helpful for further experiments, such as cloning of the gene governing the sensitivity to ether anesthesia in mice. ..
- Bonin R, Zurek A, Yu J, Bayliss D, Orser B. Hyperpolarization-activated current (In) is reduced in hippocampal neurons from Gabra5-/- mice. PLoS ONE. 2013;8:e58679 pubmed publisher..Here, we report that in mice that lack the ?5 subunit gene (Gabra5-/-), cultured embryonic hippocampal pyramidal neurons and ex vivo CA1 hippocampal neurons unexpectedly exhibited a ..
- Loebrich S, Bähring R, Katsuno T, Tsukita S, Kneussel M. Activated radixin is essential for GABAA receptor alpha5 subunit anchoring at the actin cytoskeleton. EMBO J. 2006;25:987-99 pubmed..Our data suggest radixin to represent a critical factor in receptor localization and/or downstream signaling. ..
- Ralvenius W, Benke D, AcuÃ±a M, Rudolph U, Zeilhofer H. Analgesia and unwanted benzodiazepine effects in point-mutated mice expressing only one benzodiazepine-sensitive GABAA receptor subtype. Nat Commun. 2015;6:6803 pubmed publisher..These findings should foster the development of innovative subtype-selective BDZs for novel indications such as chronic pain. ..