Glra1

Summary

Gene Symbol: Glra1
Description: glycine receptor, alpha 1 subunit
Alias: nmf11, oscillator, spasmodic, spd, glycine receptor subunit alpha-1, glycine receptor 48 kDa subunit, glycine receptor strychnine-binding subunit
Species: mouse
Products:     Glra1

Top Publications

  1. Oertel J, Villmann C, Kettenmann H, Kirchhoff F, Becker C. A novel glycine receptor beta subunit splice variant predicts an unorthodox transmembrane topology. Assembly into heteromeric receptor complexes. J Biol Chem. 2007;282:2798-807 pubmed
    ..Rather, the high level of expression in non-neuronal cells having intimate contact with synaptic regions may account for a yet unknown function of this splice variant betaDelta7 in glycinergic neurotransmission. ..
  2. Muller E, Le Corronc H, Scain A, Triller A, Legendre P. Despite GABAergic neurotransmission, GABAergic innervation does not compensate for the defect in glycine receptor postsynaptic aggregation in spastic mice. Eur J Neurosci. 2008;27:2529-41 pubmed publisher
    ..They also indicate that GABAergic neurotransmission does not compensate for defects in GlyR postsynaptic aggregation leading to spastic syndrome in C57BL/6J SPA mice. ..
  3. Imboden M, Devignot V, Goblet C. Phylogenetic relationships and chromosomal location of five distinct glycine receptor subunit genes in the teleost Danio rerio. Dev Genes Evol. 2001;211:415-22 pubmed
    ..Finally, we report that a linked pair of genes on human chromosome 4 (alpha3 and beta) is also linked on linkage group 1 in zebrafish (alphaZ3 and betaZ) as a consequence of a mosaic conserved syntheny. ..
  4. Kling C, Koch M, Saul B, Becker C. The frameshift mutation oscillator (Glra1(spd-ot)) produces a complete loss of glycine receptor alpha1-polypeptide in mouse central nervous system. Neuroscience. 1997;78:411-7 pubmed
    Mice homozygous for the recessive mutation oscillator (Glra1(spd-ot)) suffer from a complex motor disorder leading to death within three weeks after birth...
  5. Ryan S, Dixon M, Nigro M, Kelts K, Markand O, Terry J, et al. Genetic and radiation hybrid mapping of the hyperekplexia region on chromosome 5q. Am J Hum Genet. 1992;51:1334-43 pubmed
    ..RH mapping eliminated the candidate genes GABRA1 and GABRG2, which encode GABA-A receptor components, by showing that they are telomeric to the target region...
  6. Traka M, Seburn K, Popko B. Nmf11 is a novel ENU-induced mutation in the mouse glycine receptor alpha 1 subunit. Mamm Genome. 2006;17:950-5 pubmed
    b>Nmf11 is an N-ethyl-N-nitrosourea-induced recessive mouse mutation. In this article we show that the mutation is in the gene that encodes the glycine receptor alpha 1 subunit (Glra1)...
  7. Büsselberg D, Bischoff A, Becker K, Becker C, Richter D. The respiratory rhythm in mutant oscillator mice. Neurosci Lett. 2001;316:99-102 pubmed
    ..the hypothesis that the loss of glycine receptors during postnatal development (P17-P23) of homozygous mutant oscillator mice (spd(ot)/spd(ot)) may result in serious impairment of respiratory rhythm...
  8. Zhang C, Rompani S, Roska B, McCall M. Adeno-associated virus-RNAi of GlyRα1 and characterization of its synapse-specific inhibition in OFF alpha transient retinal ganglion cells. J Neurophysiol. 2014;112:3125-37 pubmed publisher
    ..Comparisons of responses in PV5 RGCs infected with AAV-scrambled-short hairpin RNA (shRNA) or AAV-Glra1-shRNA confirm a role for GlyRα1 in crossover inhibition in cone-driven circuits...
  9. Xiong W, Chen S, He L, Cheng K, Zhao Y, Chen H, et al. Presynaptic glycine receptors as a potential therapeutic target for hyperekplexia disease. Nat Neurosci. 2014;17:232-9 pubmed publisher
    ..Thus, presynaptic ?1 GlyRs emerge as a potential therapeutic target for dominant hyperekplexia disease and other diseases with GlyR deficiency. ..

More Information

Publications61

  1. Sato Y, Son J, Tucker R, Meizel S. The zona pellucida-initiated acrosome reaction: defect due to mutations in the sperm glycine receptor/Cl(-) channel. Dev Biol. 2000;227:211-8 pubmed
    ..Here, sperm from mice with mutations in the neuronal GlyR alpha or beta subunits (spasmodic and spastic) were shown to be deficient in their ability to undergo the AR initiated in vitro by glycine or by ..
  2. Blednov Y, Benavidez J, Homanics G, Harris R. Behavioral characterization of knockin mice with mutations M287L and Q266I in the glycine receptor ?1 subunit. J Pharmacol Exp Ther. 2012;340:317-29 pubmed publisher
    ..Thus, in addition to reducing ethanol action on the GlyRs, these mutations reduced glycinergic inhibition, which may also alter sensitivity to GABAergic drugs...
  3. Caraiscos V, Bonin R, Newell J, Czerwinska E, MacDonald J, Orser B. Insulin increases the potency of glycine at ionotropic glycine receptors. Mol Pharmacol. 2007;71:1277-87 pubmed
    ..Together, these results show that insulin has a novel regulatory action on the potency of glycine for ionotropic glycine receptors. ..
  4. Lynch J. Native glycine receptor subtypes and their physiological roles. Neuropharmacology. 2009;56:303-9 pubmed publisher
    ..Finally, agents that selectively potentiate different GlyR isoforms may be useful as therapeutic lead compounds for peripheral inflammatory pain and movement disorders such as spasticity. ..
  5. Findlay G, Phelan R, Roberts M, Homanics G, Bergeson S, Lopreato G, et al. Glycine receptor knock-in mice and hyperekplexia-like phenotypes: comparisons with the null mutant. J Neurosci. 2003;23:8051-9 pubmed
    ..a point mutation that impairs receptor function in the alpha1-subunit and compared these knock-in mice to oscillator (spdot) mice lacking functional GlyR alpha1-subunits...
  6. Holland K, Fleming M, Cheek S, Moran J, Beier D, Meisler M. De novo exon duplication in a new allele of mouse Glra1 (spasmodic). Genetics. 2006;174:2245-7 pubmed
    The novel neurological mutant Cincinatti arose by genomic duplication of exon 5 in the glycine receptor gene Glra1. The mutant transcript results in premature protein truncation...
  7. Koch M, Kling C, Becker C. Increased startle responses in mice carrying mutations of glycine receptor subunit genes. Neuroreport. 1996;7:806-8 pubmed
    ..The recessive mouse mutant spasmodic (spd) carries a missense mutation in the corresponding murine Glra1 gene which reduces the affinity of agonists ..
  8. Camp A, Lim R, Anderson W, Schofield P, Callister R, Brichta A. Attenuated glycine receptor function reduces excitability of mouse medial vestibular nucleus neurons. Neuroscience. 2010;170:348-60 pubmed publisher
    ..To this end we used three mouse strains (spastic, spasmodic, and oscillator), with well-characterized naturally occurring mutations in the inhibitory glycine receptor (GlyR)...
  9. Saul B, Schmieden V, Kling C, Mülhardt C, Gass P, Kuhse J, et al. Point mutation of glycine receptor alpha 1 subunit in the spasmodic mouse affects agonist responses. FEBS Lett. 1994;350:71-6 pubmed
    Homozygotic spasmodic (spd/spd) mice suffer from a motor disorder resembling poisoning by the glycine receptor antagonist strychnine...
  10. Kletke O, Sergeeva O, Lorenz P, Oberland S, Meier J, Hatt H, et al. New insights in endogenous modulation of ligand-gated ion channels: histamine is an inverse agonist at strychnine sensitive glycine receptors. Eur J Pharmacol. 2013;710:59-66 pubmed publisher
    ..Thus, we revealed histamine as an endogenous modulator of glycine receptors...
  11. Lane P, Eicher E. Gene order in linkage group XVI of the house mouse. J Hered. 1979;70:239-44 pubmed
    ..We conclude that LG XVI is not carried on Chr 12, and preliminary data indicates it is most likely carried on Chr 3. ..
  12. van Rens G, Geurts van Kessel A, Bloemendal H. Localization of the beta A4-crystallin gene (CRYBA4) on human chromosome 22 in the region q11.2-->q13.1. Cytogenet Cell Genet. 1992;61:180-3 pubmed
    ..By using cell hybrids containing translocated chromosome 22 segments, the localization could be refined to the region 22q11.2-->q13.1. ..
  13. Becker C, Schmieden V, Tarroni P, Strasser U, Betz H. Isoform-selective deficit of glycine receptors in the mouse mutant spastic. Neuron. 1992;8:283-9 pubmed
    ..Thus, the age-dependent manifestation of spastic symptoms after birth reflects a selective effect of the mutation on the developmental expression of the adult glycine receptor isoform. ..
  14. Villmann C, Oertel J, Ma Högemeier Z, Hollmann M, Sprengel R, Becker K, et al. Functional complementation of Glra1(spd-ot), a glycine receptor subunit mutant, by independently expressed C-terminal domains. J Neurosci. 2009;29:2440-52 pubmed publisher
    The oscillator mouse (Glra1(spd-ot)) carries a 9 bp microdeletion plus a 2 bp microinsertion in the glycine receptor alpha1 subunit gene, resulting in the absence of functional alpha1 polypeptides from the CNS and lethality 3 weeks after ..
  15. Weiss J, O Sullivan G, Heinze L, Chen H, Betz H, Wassle H. Glycinergic input of small-field amacrine cells in the retinas of wildtype and glycine receptor deficient mice. Mol Cell Neurosci. 2008;37:40-55 pubmed
    ..Glycinergic sIPSCs of NF cells had slow kinetics (tau=27+/-6.8 ms) that were significantly prolonged in Glra2-/- mice (tau=69+/-16 ms). These data show that morphologically distinct amacrine cells express different sets of GlyRs. ..
  16. Karnani M, Venner A, Jensen L, Fugger L, Burdakov D. Direct and indirect control of orexin/hypocretin neurons by glycine receptors. J Physiol. 2011;589:639-51 pubmed publisher
  17. Buerbank S, Becker K, Becker C, Brandt N, Engel J, Knipper M, et al. Developmental regulation of glycine receptors at efferent synapses of the murine cochlea. Histochem Cell Biol. 2011;136:387-98 pubmed publisher
    ..In summary, the distinct developmental regulation of GlyRs in the murine cochlea advocates a contribution of these chloride channels to efferent olivocochlear innervation. ..
  18. Aguayo L, Castro P, Mariqueo T, Muñoz B, Xiong W, Zhang L, et al. Altered sedative effects of ethanol in mice with ?1 glycine receptor subunits that are insensitive to G?? modulation. Neuropsychopharmacology. 2014;39:2538-48 pubmed publisher
    ..5 g/Kg). These data provide the first evidence to link a molecular site in the GlyR with the sedative effects produced by intoxicating doses of ethanol. ..
  19. Schaefer N, Berger A, van Brederode J, Zheng F, Zhang Y, Leacock S, et al. Disruption of a Structurally Important Extracellular Element in the Glycine Receptor Leads to Decreased Synaptic Integration and Signaling Resulting in Severe Startle Disease. J Neurosci. 2017;37:7948-7961 pubmed publisher
    ..The GlyR β8-β9 loop is therefore an essential regulator of conformational rearrangements during ion channel opening and closing. ..
  20. Graham B, Schofield P, Sah P, Callister R. Altered inhibitory synaptic transmission in superficial dorsal horn neurones in spastic and oscillator mice. J Physiol. 2003;551:905-16 pubmed
    The spastic (spa) and oscillator (ot) mouse have naturally occurring mutations in the inhibitory glycine receptor (GlyR) and exhibit severe motor disturbances when exposed to unexpected sensory stimuli...
  21. Shiang R, Ryan S, Zhu Y, Hahn A, O Connell P, Wasmuth J. Mutations in the alpha 1 subunit of the inhibitory glycine receptor cause the dominant neurologic disorder, hyperekplexia. Nat Genet. 1993;5:351-8 pubmed
    ..describe the identification of point mutations in the gene encoding the alpha 1 subunit of the glycine receptor (GLRA1) in STHE patients from four different families...
  22. Heck S, Enz R, Richter Landsberg C, Blohm D. Expression and mRNA splicing of glycine receptor subunits and gephyrin during neuronal differentiation of P19 cells in vitro, studied by RT-PCR and immunocytochemistry. Brain Res Dev Brain Res. 1997;98:211-20 pubmed
    ..In conclusion, P19 and primary neuronal cells but not PC12 cells express the transcripts of glycine receptor components, necessary to generate functional receptors. ..
  23. Feng G, Tintrup H, Kirsch J, Nichol M, Kuhse J, Betz H, et al. Dual requirement for gephyrin in glycine receptor clustering and molybdoenzyme activity. Science. 1998;282:1321-4 pubmed
    ..The mutant phenotype resembled that of humans with hereditary molybdenum cofactor deficiency and hyperekplexia (a failure of inhibitory neurotransmission), suggesting that gephyrin function may be impaired in both diseases. ..
  24. Plappert C, Pilz P, Becker K, Becker C, Schnitzler H. Increased sensitization of acoustic startle response in spasmodic mice with a mutation of the glycine receptor alpha1-subunit gene. Behav Brain Res. 2001;121:57-67 pubmed
    The spontaneous mutant mouse spasmodic (spd) carries a missense mutation affecting the glycine receptor alpha1-subunit gene. This results in a decreased binding affinity to glycine...
  25. Buckwalter M, Cook S, Davisson M, White W, Camper S. A frameshift mutation in the mouse alpha 1 glycine receptor gene (Glra1) results in progressive neurological symptoms and juvenile death. Hum Mol Genet. 1994;3:2025-30 pubmed
    The neurologic mutant mouse, oscillator, is characterized by a fine motor tremor and muscle spasms that begin at 2 weeks of age and progressively worsen, resulting in death by 3 weeks of age...
  26. Matzenbach B, Maulet Y, Sefton L, Courtier B, Avner P, Guenet J, et al. Structural analysis of mouse glycine receptor alpha subunit genes. Identification and chromosomal localization of a novel variant. J Biol Chem. 1994;269:2607-12 pubmed
    ..Like the alpha 2 gene, the alpha 4 gene maps to the mouse X chromosome. Our data indicate that the genomic organization of glycine receptor alpha subunit genes is conserved during evolution. ..
  27. Adams R, Sato K, Shimada S, Tohyama M, Puschel A, Betz H. Gene structure and glial expression of the glycine transporter GlyT1 in embryonic and adult rodents. J Neurosci. 1995;15:2524-32 pubmed
    ..In the adult rat brain and spinal cord, GlyT1 hybridization signals were found exclusively in glial cells. Our data indicate that GlyT1 is an early marker of neural development and encodes glia-specific transporter proteins. ..
  28. Unterer B, Becker C, Villmann C. The importance of TM3-4 loop subdomains for functional reconstitution of glycine receptors by independent domains. J Biol Chem. 2012;287:39205-15 pubmed publisher
    ..Thus, residues 357-418 represent an important determinant in the process of conformational rearrangements following ligand binding resulting in channel opening. ..
  29. Simon E. Phenotypic heterogeneity and disease course in three murine strains with mutations in genes encoding for alpha 1 and beta glycine receptor subunits. Mov Disord. 1997;12:221-8 pubmed
    ..autosomal recessive mutant mouse strains with single-gene mutations affecting either the alpha 1 (spasmodic and oscillator) or beta (spastic) subunits of the glycine receptor were studied...
  30. Borghese C, Blednov Y, Quan Y, Iyer S, Xiong W, Mihic S, et al. Characterization of two mutations, M287L and Q266I, in the ?1 glycine receptor subunit that modify sensitivity to alcohols. J Pharmacol Exp Ther. 2012;340:304-16 pubmed publisher
    ..The behavioral characterization of these knockin mice is presented in a companion article (J Pharmacol Exp Ther 340:317-329, 2012). ..
  31. Ivanova E, Müller U, Wässle H. Characterization of the glycinergic input to bipolar cells of the mouse retina. Eur J Neurosci. 2006;23:350-64 pubmed
    ..Patch-clamp recordings were performed from retinal slices of wild-type, GlyRalpha1-deficient (Glra1(spd-ot)) and GlyRalpha3-deficient (Glra3(-/-)) mice...
  32. Jin K, Jiang H, Mo Z, Xiang M. Early B-cell factors are required for specifying multiple retinal cell types and subtypes from postmitotic precursors. J Neurosci. 2010;30:11902-16 pubmed publisher
  33. McCracken L, Blednov Y, Trudell J, Benavidez J, Betz H, Harris R. Mutation of a zinc-binding residue in the glycine receptor ?1 subunit changes ethanol sensitivity in vitro and alcohol consumption in vivo. J Pharmacol Exp Ther. 2013;344:489-500 pubmed publisher
    ..Next, we evaluated the in vivo effects of the D80A substitution by using heterozygous Glra1(D80A) knock-in (KI) mice...
  34. Lane P, Ganser A, Kerner A, White W. Spasmodic, a mutation on chromosome 11 in the mouse. J Hered. 1987;78:353-6 pubmed
    A new recessive mutation, spasmodic (spd), producing behavior that mimics that of the neurological mutation spastic (spa) with rapid tremors, stiff posture, and difficulty in righting, arose spontaneously in strain A/HeJ at the Jackson ..
  35. Kunz P, Burette A, Weinberg R, Philpot B. Glycine receptors support excitatory neurotransmitter release in developing mouse visual cortex. J Physiol. 2012;590:5749-64 pubmed publisher
    ..Our findings demonstrate a developmentally regulated mechanism for controlling excitatory neurotransmitter release in the neocortex. ..
  36. Kingsmore S, Giros B, Suh D, Bieniarz M, Caron M, Seldin M. Glycine receptor beta-subunit gene mutation in spastic mouse associated with LINE-1 element insertion. Nat Genet. 1994;7:136-41 pubmed
    ..These results provide evidence that Glrb is necessary for postsynaptic expression of glycine receptor complexes, and suggest Glrb as a candidate gene for inherited myoclonus in other species. ..
  37. Graham B, Tadros M, Schofield P, Callister R. Probing glycine receptor stoichiometry in superficial dorsal horn neurones using the spasmodic mouse. J Physiol. 2011;589:2459-74 pubmed publisher
    ..Here we use the spasmodic mouse, which has a naturally occurring mutation (A52S) in the ?1 subunit of the GlyR, to examine the effect of ..
  38. Markstahler U, Kremer E, Kimmina S, Becker K, Richter D. Effects of functional knock-out of alpha 1 glycine-receptors on breathing movements in oscillator mice. Respir Physiol Neurobiol. 2002;130:33-42 pubmed
    ..of glycinergic inhibition deriving from mutations of the glycine-receptor gene Glra1 on the breathing pattern of oscillator mice were studied...
  39. Chambers D, Wilson L, Alfonsi F, Hunter E, Saxena U, Blanc E, et al. Rhombomere-specific analysis reveals the repertoire of genetic cues expressed across the developing hindbrain. Neural Dev. 2009;4:6 pubmed publisher
    ..These findings give the first genome-wide insight into the complexity of gene expression during patterning of the developing hindbrain. ..
  40. Watkins Chow D, Buckwalter M, Newhouse M, Lossie A, Brinkmeier M, Camper S. Genetic mapping of 21 genes on mouse chromosome 11 reveals disruptions in linkage conservation with human chromosome 5. Genomics. 1997;40:114-22 pubmed
    ..Comparison of the mouse and human maps with data for other species provides an emerging picture of mammalian chromosome evolution. ..
  41. Graham B, Schofield P, Sah P, Margrie T, Callister R. Distinct physiological mechanisms underlie altered glycinergic synaptic transmission in the murine mutants spastic, spasmodic, and oscillator. J Neurosci. 2006;26:4880-90 pubmed
    Spastic (spa), spasmodic (spd), and oscillator (ot) mice have naturally occurring glycine receptor (GlyR) mutations, which manifest as motor deficits and an exaggerated "startle response...
  42. Majumdar S, Weiss J, Wässle H. Glycinergic input of widefield, displaced amacrine cells of the mouse retina. J Physiol. 2009;587:3831-49 pubmed publisher
    ..The studies were performed in wild-type mice and in mutant mice deficient in the GlyRalpha1 (Glra1(spd-ot), 'oscillator' mouse), the GlyRalpha2 (Glra2(-/-)) and the GlyRalpha3 subunit (Glra3(-/-))...
  43. Mordel J, Karnas D, Inyushkin A, Challet E, Pevet P, Meissl H. Activation of glycine receptor phase-shifts the circadian rhythm in neuronal activity in the mouse suprachiasmatic nucleus. J Physiol. 2011;589:2287-300 pubmed publisher
    ..Both effects were suppressed by strychnine or by PMBA. These results suggest that glycine is able to modulate circadian activity by acting directly on its specific receptors in SCN neurons. ..
  44. Ryan S, Buckwalter M, Lynch J, Handford C, Segura L, Shiang R, et al. A missense mutation in the gene encoding the alpha 1 subunit of the inhibitory glycine receptor in the spasmodic mouse. Nat Genet. 1994;7:131-5 pubmed
    ..b>Spasmodic (spd), a recessive neurologic mouse mutant, resembles hyperekplexia phenotypically, and the two disease loci map ..
  45. Hirzel K, Müller U, Latal A, Hülsmann S, Grudzinska J, Seeliger M, et al. Hyperekplexia phenotype of glycine receptor alpha1 subunit mutant mice identifies Zn(2+) as an essential endogenous modulator of glycinergic neurotransmission. Neuron. 2006;52:679-90 pubmed
    ..by producing knockin mice carrying the mutation D80A in the glycine receptor (GlyR) alpha1 subunit gene (Glra1). This substitution selectively eliminates the potentiating effect of Zn(2+) on GlyR currents...
  46. Li J, Blankenship M, Baccei M. Deficits in glycinergic inhibition within adult spinal nociceptive circuits after neonatal tissue damage. Pain. 2013;154:1129-39 pubmed publisher
    ..These findings suggest that aberrant sensory input during early life has permanent consequences for the functional organization of nociceptive synaptic circuits within the adult spinal cord. ..
  47. Zhao M, Hülsmann S, Winter S, Dutschmann M, Richter D. Calcium-regulated potassium currents secure respiratory rhythm generation after loss of glycinergic inhibition. Eur J Neurosci. 2006;24:145-54 pubmed
    Mutant oscillator mice (Glra1(spd -/-)) are characterized by a developmental loss of glycinergic inhibition...
  48. Lane P. Two new mutations in linkage group XVI of the house mouse. Flaky tail and varitint-waddler-J. J Hered. 1972;63:135-40 pubmed
  49. Moran J, Bolton A, Tran P, Brown A, Dwyer N, Manning D, et al. Utilization of a whole genome SNP panel for efficient genetic mapping in the mouse. Genome Res. 2006;16:436-40 pubmed
    ..By using this approach, we identified DNA sequence changes in two ethylnitrosourea-induced mutants. ..
  50. Buckwalter M, Testa C, Noebels J, Camper S. Genetic mapping and evaluation of candidate genes for spasmodic, a neurological mouse mutation with abnormal startle response. Genomics. 1993;17:279-86 pubmed
    b>Spasmodic (spd) is a recessive mouse mutation characterized by a prolonged righting reflex, fine motor tremor, leg clasping, and stiffness...
  51. Cui Z, Yokoi N, Kuramoto T, Kitada K, Serikawa T. Extension of conserved regions in the rat and mouse genomes by chromosomal assignments of 29 rat genes. Exp Anim. 1998;47:83-8 pubmed
    ..In addition, four conserved regions were newly revealed. The method described in this study appears to be simple and efficient for constructing a whole genome comparative map of the rat and mouse. ..
  52. Becker L, von Wegerer J, Schenkel J, Zeilhofer H, Swandulla D, Weiher H. Disease-specific human glycine receptor alpha1 subunit causes hyperekplexia phenotype and impaired glycine- and GABA(A)-receptor transmission in transgenic mice. J Neurosci. 2002;22:2505-12 pubmed