Mutation in the Scyl1 gene encoding amino-terminal kinase-like protein causes a recessive form of spinocerebellar neurodegeneration
Mutation in the Scyl1 gene encoding amino-terminal kinase-like protein causes a recessive form of spinocerebellar neurodegeneration
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DOI：
10.1038/sj.embor.7401001
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发表时间：
2007-07-01
期刊：
影响因子：
7.7
通讯作者：
Bittner, Reginald E.
中科院分区：
文献类型：
--
作者：
Schmidt, Wolfgang M.;Kraus, Cornelia;Bittner, Reginald E.
在这里，我们证明了小鼠神经退行性疾病MDF(常染色体隐性突变的小鼠‘肌肉缺陷’)是由Scyl1功能缺失突变引起的，该突变扰乱了N端蛋白的表达，N端蛋白是核质运输机制中一个进化上保守的假定成分。Scyl1在神经元中有显著表达，在中枢神经系统突触和神经肌肉接头处有丰富表达。我们认为MDF的病理包括小脑萎缩、浦肯野细胞丢失和视神经萎缩，从而建立了一种新的人类小脑受累的神经退行性疾病的动物模型。
Here, we show that the murine neurodegenerative disease mdf ( autosomal recessive mouse mutant 'muscle deficient') is caused by a loss-of-function mutation in Scyl1, disrupting the expression of N-terminal kinase-like protein, an evolutionarily conserved putative component of the nucleocytoplasmic transport machinery. Scyl1 is prominently expressed in neurons, and enriched at central nervous system synapses and neuromuscular junctions. We show that the pathology of mdf comprises cerebellar atrophy, Purkinje cell loss and optic nerve atrophy, and therefore defines a new animal model for neurodegenerative diseases with cerebellar involvement in humans.