Glycine receptor beta-subunit gene mutation in spastic mouse associated with LINE-1 element insertion.
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.
Kingsmore
S F
SF
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Giros
B
B
Suh
D
D
Bieniarz
M
M
Caron
M G
MG
Seldin
M F
MF
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
D018076:DNA, Complementary; D018009:Receptors, Glycine; D018626:Retroelements