spastic

Summary

Gene Symbol: spastic
Description: glycine receptor, beta subunit
Alias: AI853901, Glyrb, spa, spastic, glycine receptor subunit beta, glycine receptor 58 kDa subunit, inhibitory glycine receptor
Species: mouse
Products:     spastic

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
    The inhibitory glycine receptor is a ligand-gated ion channel with a pentameric assembly from ligand binding alpha and structural beta subunits...
  2. 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
    b>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...
  3. Molon A, Di Giovanni S, Hathout Y, Natale J, Hoffman E. Functional recovery of glycine receptors in spastic murine model of startle disease. Neurobiol Dis. 2006;21:291-304 pubmed
    ..Here, we used the homozygous spastic (spa) mutant mice, which resemble human hereditary hyperekplexia, to determine the molecular remodeling of the ..
  4. von Wegerer J, Becker K, Glockenhammer D, Becker C, Zeilhofer H, Swandulla D. Spinal inhibitory synaptic transmission in the glycine receptor mouse mutant spastic. Neurosci Lett. 2003;345:45-8 pubmed
    b>Inhibitory glycine receptor (GlyR) and GABA(A) receptor (GABA(A)R)-mediated synaptic transmission was examined in two strains of the GlyR mutant mouse spastic and the respective wild types...
  5. 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
    ..In spastic mice (SPA), a model of human hyperekplexic syndrome, an insertion into the gene of the glycine receptor (GlyR) ..
  6. 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. ..
  7. White W, Heller A. Glycine receptor alteration in the mutant mouse spastic. Nature. 1982;298:655-7 pubmed
  8. Hartenstein B, Schenkel J, Kuhse J, Besenbeck B, Kling C, Becker C, et al. Low level expression of glycine receptor beta subunit transgene is sufficient for phenotype correction in spastic mice. EMBO J. 1996;15:1275-82 pubmed
    Mutations in inhibitory glycine receptor (GlyR) subunit genes are associated with neuromotor diseases in man and mouse...
  9. 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
    ..The recessive mouse mutation spastic (spa) is a prototype of inherited myoclonus...

More Information

Publications52

  1. Mülhardt C, Fischer M, Gass P, Simon Chazottes D, Guenet J, Kuhse J, et al. The spastic mouse: aberrant splicing of glycine receptor beta subunit mRNA caused by intronic insertion of L1 element. Neuron. 1994;13:1003-15 pubmed
    Mice homozygous for the spastic mutation (spa) suffer from a complex motor disorder resulting from reduced CNS levels of the adult glycine receptor isoform GlyRA, which is composed of ligand-binding alpha 1 and structural beta ..
  2. Becker K, Braune M, Benderska N, Buratti E, Baralle F, Villmann C, et al. A retroelement modifies pre-mRNA splicing: the murine Glrb(spa) allele is a splicing signal polymorphism amplified by long interspersed nuclear element insertion. J Biol Chem. 2012;287:31185-94 pubmed publisher
    The glycine receptor-deficient mutant mouse spastic carries a full-length long interspersed nuclear element (LINE1) retrotransposon in intron 6 of the glycine receptor ? subunit gene, Glrb(spa)...
  3. 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
    ..All mutations occur in the same base pair of exon 6 and result in the substitution of an uncharged amino acid (leucine or glutamine) for Arg271 in the mature protein. ..
  4. Koch M, Kling C, Becker C. Increased startle responses in mice carrying mutations of glycine receptor subunit genes. Neuroreport. 1996;7:806-8 pubmed
    An exaggerated startle response caused by mutations of the alpha 1 subunit gene of the inhibitory glycine receptor (GLRA1) is the key symptom of human hyperekplexia or startle disease...
  5. Lane P, Eicher E. Gene order in linkage group XVI of the house mouse. J Hered. 1979;70:239-44 pubmed
    ..The map of LG XVI is as follows: spa-3-ma-2-ft-1-soc-6-op-3-(Amy-1, Amy-2)-20-Va with the position of de known to be on the ma side of Va...
  6. 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 this system the expression of the alpha (alpha 1-alpha 3) and beta subunits of the inhibitory glycine receptor (GlyR) and of gephyrin as well as their mRNA splice variants was analyzed by RT-PCR and by ..
  7. 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
    ..spastic, spasmodic, and oscillator), with well-characterized naturally occurring mutations in the inhibitory glycine receptor (GlyR)...
  8. Yazulla S, Studholme K, Pinto L. Differences in the retinal GABA system among control, spastic mutant and retinal degeneration mutant mice. Vision Res. 1997;37:3471-82 pubmed
    Immunocytochemical methods were used to compare the GABA system in control mice and two mutant strains: spastic which has reduced glycine receptors and retinal degeneration mutant in which the photoreceptors degenerate and reportedly ..
  9. Naas T, DeBerardinis R, Moran J, Ostertag E, Kingsmore S, Seldin M, et al. An actively retrotransposing, novel subfamily of mouse L1 elements. EMBO J. 1998;17:590-7 pubmed
    ..Recent insertions of two full-length L1s, L1spa and L1Orl, caused the disease phenotypes of the spastic and Orleans reeler mice respectively...
  10. del Pino I, Koch D, Schemm R, Qualmann B, Betz H, Paarmann I. Proteomic analysis of glycine receptor ? subunit (GlyR?)-interacting proteins: evidence for syndapin I regulating synaptic glycine receptors. J Biol Chem. 2014;289:11396-409 pubmed publisher
    ..Similar changes in GlyR cluster properties were found in spinal cultures from SdpI-deficient mice. Our results are consistent with a role of SdpI in the trafficking and/or cytoskeletal anchoring of synaptic GlyRs. ..
  11. Cosgrove A, Graham H. Botulinum toxin A prevents the development of contractures in the hereditary spastic mouse. Dev Med Child Neurol. 1994;36:379-85 pubmed
    The hereditary spastic mouse was studied as a model of cerebral palsy in childhood to test the hypothesis that intramuscular botulinum toxin A would prevent the development of calf-muscle contractures...
  12. Eom T, Zhang C, Wang H, Lay K, Fak J, Noebels J, et al. NOVA-dependent regulation of cryptic NMD exons controls synaptic protein levels after seizure. elife. 2013;2:e00178 pubmed publisher
    ..The data reveal a hidden means of dynamic RNA regulation linking electrical activity to splicing and protein output, and of mediating homeostatic excitation/inhibition balance in neurons.DOI:http://dx.doi.org/10.7554/eLife.00178.001. ..
  13. Roberts E, Kuriyama K. Biochemical-physiological correlations in studies of the gamma-aminobutyric acid system. Brain Res. 1968;8:1-35 pubmed
  14. Becker L, Hartenstein B, Schenkel J, Kuhse J, Betz H, Weiher H. Transient neuromotor phenotype in transgenic spastic mice expressing low levels of glycine receptor beta-subunit: an animal model of startle disease. Eur J Neurosci. 2000;12:27-32 pubmed
    ..or hereditary hyperekplexia has been shown to result from mutations in the alpha1-subunit gene of the inhibitory glycine receptor (GlyR)...
  15. 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 solubilized ZP ..
  16. Kneussel M, Engelkamp D, Betz H. Distribution of transcripts for the brain-specific GDP/GTP exchange factor collybistin in the developing mouse brain. Eur J Neurosci. 2001;13:487-92 pubmed
    ..Our data show that collybistin expression is upregulated when neurons become postmitotic and start to differentiate. ..
  17. Meier H, Chai C. Spastic, an hereditary neurological mutation in the mouse characterized by vertebral arthropathy and leptomeningeal cyst formation. Exp Med Surg. 1970;28:24-38 pubmed
  18. White W. The glycine receptor in the mutant mouse spastic (spa): strychnine binding characteristics and pharmacology. Brain Res. 1985;329:1-6 pubmed
    ..is a marked deficit in the binding of the glycine receptor antagonist strychnine to the CNS of the mutant mouse spastic. The characteristics and pharmacology of [3H]strychnine binding to washed homogenates of spastic and littermate ..
  19. 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
    The mutant mouse spastic (spa) develops a characteristic motor disorder about 2 weeks after birth, with symptoms resembling sublethal poisoning by the glycinergic antagonist strychnine...
  20. 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. ..
  21. Schaefer N, Vogel N, Villmann C. Glycine receptor mutants of the mouse: what are possible routes of inhibitory compensation?. Front Mol Neurosci. 2012;5:98 pubmed publisher
    ..The mutations either localized in the ? (spasmodic, oscillator, cincinnati, Nmf11) or the ? (spastic) subunit of the glycine receptor (GlyR) are much less tolerated in mice than in humans, leaving the question for ..
  22. Xu H, Tian N. Glycine receptor-mediated synaptic transmission regulates the maturation of ganglion cell synaptic connectivity. J Comp Neurol. 2008;509:53-71 pubmed publisher
    ..for OFF RGC dendritic development, the light-evoked responses and dendritic stratification patterns of RGCs in Spastic mutant mice, in which the OFF signal transmission in the rod pathway is largely blocked due to a reduction of ..
  23. 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. ..
  24. Winkelmann A, You X, Grünewald N, Häussler U, Krestel H, Haas C, et al. Identification of a new genomic hot spot of evolutionary diversification of protein function. PLoS ONE. 2015;10:e0125413 pubmed publisher
    ..This study identifies a new genomic hot spot which contributes to phylogenetic diversification of protein function and advances our understanding of phylogenetic relationships. ..
  25. Eicher E, Womack J. Chromosomal location of soluble glutamic-pyruvic transaminase-1 (Gpt-1) in the mouse. Biochem Genet. 1977;15:1-8 pubmed
    ..This is an improvement over previous methods that produced bands of nonfluorescence against a fluorescent background. ..
  26. Sato Y, Tucker R, Meizel S. Detection of glycine receptor/Cl- channel beta subunit transcripts in mouse testis. Zygote. 2002;10:105-8 pubmed
    ..In situ hybridisation analysis demonstrated that GlyR beta subunit mRNAs were expressed within the germ cells of seminiferous tubules in those mice. ..
  27. 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. ..
  28. Kingsmore S, Spicer A, Gendler S, Seldin M. Genetic mapping of the tumor-associated mucin 1 gene on mouse chromosome 3. Mamm Genome. 1995;6:378-9 pubmed
  29. Chai C, Roberts E, Sidman R. Influence of aminooxyacetic acid, a gamma-aminobutyrate transaminase inhibitor, on hereditary spastic defect in the mouse. Proc Soc Exp Biol Med. 1962;109:491-5 pubmed
  30. Zita M, Marchionni I, Bottos E, Righi M, Del Sal G, Cherubini E, et al. Post-phosphorylation prolyl isomerisation of gephyrin represents a mechanism to modulate glycine receptors function. EMBO J. 2007;26:1761-71 pubmed
    ..Our results suggest that phosphorylation-dependent prolyl isomerisation of gephyrin represents a mechanism for regulating GlyRs function. ..
  31. 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
  32. Eichler S, Förstera B, Smolinsky B, Jüttner R, Lehmann T, Fähling M, et al. Splice-specific roles of glycine receptor alpha3 in the hippocampus. Eur J Neurosci. 2009;30:1077-91 pubmed publisher
  33. 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
    ..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...
  34. Handford C, Lynch J, Baker E, Webb G, Ford J, Sutherland G, et al. The human glycine receptor beta subunit: primary structure, functional characterisation and chromosomal localisation of the human and murine genes. Brain Res Mol Brain Res. 1996;35:211-9 pubmed
    The inhibitory glycine receptor (GlyR) is a pentameric receptor comprised of alpha and beta subunits, of which the beta subunit has not been characterised in humans...
  35. Specht C, Grünewald N, Pascual O, Rostgaard N, Schwarz G, Triller A. Regulation of glycine receptor diffusion properties and gephyrin interactions by protein kinase C. EMBO J. 2011;30:3842-53 pubmed publisher
    ..We propose that the regulation of GlyR dynamics by PKC thus contributes to the plasticity of inhibitory synapses and may be involved in maladaptive forms of synaptic plasticity. ..
  36. Pinto L, Grunert U, Studholme K, Yazulla S, Kirsch J, Becker C. Glycine receptors in the retinas of normal and spastic mutant mice. Invest Ophthalmol Vis Sci. 1994;35:3633-9 pubmed
    b>Spastic mutant mice have abnormal gait and righting behavior, and the responses of their retinal ganglion cells have recently been shown to be abnormal...
  37. Manceau V, Kremmer E, Nabel E, Maucuer A. The protein kinase KIS impacts gene expression during development and fear conditioning in adult mice. PLoS ONE. 2012;7:e43946 pubmed publisher
    ..This difference suggests that disregulation of gene expression due to KIS inactivation affects specific brain functions. ..
  38. Stone C, Pinto L. Receptive field organization of retinal ganglion cells in the spastic mutant mouse. J Physiol. 1992;456:125-42 pubmed
    1. We examined the receptive field properties of retinal ganglion cells in the isolated, superfused retinae of spastic mutant mice (B6C3Fe-spa/spa) that did not have the retinal degeneration (rd) phenotype...
  39. 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. ..
  40. 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. ..
  41. 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
  42. Tintrup H, Fischer M, Betz H, Kuhse J. Exonic Sp1 sites are required for neural-specific expression of the glycine receptor beta subunit gene. Biochem J. 2001;355:179-87 pubmed
    The gene encoding the beta subunit of the inhibitory glycine receptor (GlyR) is widely expressed throughout the mammalian central nervous system...
  43. 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...