Brown A, Bernier G, Mathieu M, Rossant J, Kothary R
Institut du cancer de Montréal, Centre de Recherche L.-C. Simard, Québec, Canada.
Nat Genet. 1995 Jul;10(3):301-6. doi: 10.1038/ng0795-301.
Dystonia musculorum (dt) is a hereditary neurodegenerative disease in mice that leads to a sensory ataxia. We describe cloning of a candidate dt gene, dystonin, that is predominantly expressed in the dorsal root ganglia and other sites of neurodegeneration in dt mice. Dystonin encodes an N-terminal actin binding domain and a C-terminal portion comprised of the hemidesmosomal protein, bullous pemphigoid antigen 1 (bpag1). dt and bpag1 are part of the same transcription unit which is partially deleted in a transgenic strain of mice, Tg4, that harbours an insertional mutation at the dt locus, and in mice that carry a spontaneous dt mutation, dtAlb. We also demonstrate abnormal dystonin transcripts in a second dt mutant, dt24J. We conclude that mutations in the dystonin gene are the primary genetic lesion in dt mice.
肌张力障碍小鼠（dt）是一种导致感觉性共济失调的遗传性神经退行性疾病。我们描述了一个候选dt基因——网蛋白（dystonin）的克隆，该基因主要在dt小鼠的背根神经节和其他神经退行性变部位表达。网蛋白编码一个N端肌动蛋白结合结构域和一个由半桥粒蛋白——大疱性类天疱疮抗原1（bpag1）组成的C端部分。dt和bpag1是同一转录单位的一部分，在携带dt位点插入突变的转基因小鼠品系Tg4以及携带自发dt突变dtAlb的小鼠中，该转录单位被部分缺失。我们还在第二个dt突变体dt24J中证实了网蛋白转录本异常。我们得出结论，网蛋白基因的突变是dt小鼠的主要遗传损伤。
