Ordway J M, Cearley J A, Detloff P J
Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham 35294, USA.
Philos Trans R Soc Lond B Biol Sci. 1999 Jun 29;354(1386):1083-8. doi: 10.1098/rstb.1999.0463.
Several neurological disorders have been attributed to the inheritance of long CAG-polyglutamine repeats. Unlike classical mutations, whose deleterious effects are totally dependent on the context of the gene in which they reside, these translated CAG repeat mutations have been shown to cause neurotoxicity and neuronal intranuclear inclusions when expressed outside their natural gene context. We provide a description of mice with different lengths of repeat in the foreign context of the murine Hprt locus, focusing on aspects of the phenotype that provide an insight into the mechanism by which this unusual mutation might cause toxicity.
几种神经系统疾病被认为与长CAG-聚谷氨酰胺重复序列的遗传有关。与经典突变不同，经典突变的有害效应完全取决于它们所在基因的背景，而这些翻译后的CAG重复突变已被证明在其天然基因背景之外表达时会导致神经毒性和神经元核内包涵体形成。我们描述了在小鼠次黄嘌呤磷酸核糖转移酶（Hprt）基因座的外源背景下具有不同重复长度的小鼠，重点关注表型方面，这些方面有助于深入了解这种异常突变可能导致毒性的机制。
