title: Glycine receptor beta-subunit gene mutation in spastic mouse associated with LINE-1 element insertion.
abstract: Congenital myoclonus is a widespread neurologic disorder characterized by hyperexcitability, muscular spasticity and myoclonus associated with marked reduction in neural glycine binding sites. The recessive mouse mutation spastic (spa) is a prototype of inherited myoclonus. Here we show that defects in the gene encoding the beta-subunit of the glycine receptor (Glrb) underlie spa: Glrb maps to the same region of mouse chromosome 3 as spa, and Glrb mRNA is markedly reduced throughout brains of spa mice, most likely as a result of an insertional mutation of a 7.1 kilobase LINE-1 element within intron 6 of Glrb. 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.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: S F
authors.initials: SF
authors.lastname: Kingsmore
authors.forename: B
authors.initials: B
authors.lastname: Giros
authors.forename: D
authors.initials: D
authors.lastname: Suh
authors.forename: M
authors.initials: M
authors.lastname: Bieniarz
authors.forename: M G
authors.initials: MG
authors.lastname: Caron
authors.forename: M F
authors.initials: MF
authors.lastname: Seldin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression; D007438:Introns; D051379:Mice; D008818:Mice, Neurologic Mutants; D008969:Molecular Sequence Data; D009154:Mutation; D009207:Myoclonus / Q000151:congenital / Q000235:genetics; D016133:Polymerase Chain Reaction; D018009:Receptors, Glycine / Q000235:genetics* / Q000378:metabolism; D018626:Retroelements
chemical_list: D018076:DNA, Complementary; D018009:Receptors, Glycine; D018626:Retroelements