title: Disorders of the inhibitory glycine receptor: the spastic mouse.
abstract: The mutant mouse spastic suffers from a motor disorder of autosomal recessive inheritance which is characterized by tremor, myoclonic episodes, and a disturbed righting response. The most prominent alteration in the mutant is a substantial deficit of postsynaptic glycine receptor channels resulting in a dramatic reduction of glycinergic synaptic inhibition. Function and structure of the glycine receptor protein appear unaffected, which argues for a regulatory rather than a structural effect of the spastic mutation. It appears that other alterations in the spastic mouse are secondary to this fundamental disturbance in the balance of excitatory and inhibitory impulses. In particular, a significant increase in GABAA receptors of the lower parts of the CNS may serve a compensatory function, counteracting in part losses of glycinergic inhibition. Pharmacological experiments indeed show that facilitation of GABAA receptor-mediated inhibition alleviates symptoms of the spastic motor disorder. The recent cDNA cloning of glycine receptor subunits should help define the molecular mechanism by which the spastic gene causes the glycine receptor deficit.
authors.affiliation: Zentrum für Molekulare Biologie, Universität Heidelberg, Federal Republic of Germany.
authors.forename: C M
authors.initials: CM
authors.lastname: Becker
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005998:Glycine / Q000378:metabolism; D006801:Humans; D051379:Mice; D008818:Mice, Neurologic Mutants; D009069:Movement Disorders / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D009207:Myoclonus / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter / Q000235:genetics* / Q000502:physiology
chemical_list: D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter; D005998:Glycine