Kingsmore S F, Giros B, Suh D, Bieniarz M, Caron M G, Seldin M F
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Nat Genet. 1994 Jun;7(2):136-41. doi: 10.1038/ng0694-136.
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.
先天性肌阵挛是一种广泛存在的神经系统疾病，其特征为兴奋性过高、肌肉痉挛和肌阵挛，伴有神经甘氨酸结合位点显著减少。隐性小鼠突变体spastic（spa）是遗传性肌阵挛的一个原型。在此我们表明，编码甘氨酸受体β亚基（Glrb）的基因缺陷是spa的基础：Glrb定位于小鼠3号染色体上与spa相同的区域，并且在spa小鼠的整个大脑中Glrb mRNA显著减少，这很可能是由于Glrb内含子6内一个7.1千碱基的LINE-1元件插入突变所致。这些结果提供了证据，表明Glrb对于甘氨酸受体复合物的突触后表达是必需的，并提示Glrb作为其他物种遗传性肌阵挛的一个候选基因。
