Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, Canada.
Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Canada.
Biochem Biophys Res Commun. 2021 Sep 3;568:48-54. doi: 10.1016/j.bbrc.2021.06.052. Epub 2021 Jun 26.
The F115C mutation in the MATR3 gene has been linked to amyotrophic lateral sclerosis (ALS). To determine the pathogenicity of the F115C mutation and the mechanism by which this mutation causes ALS, we generated mice that harbor the F115C mutation in the endogenous murine Matr3 locus. Heterozygous or homozygous MATR3 F115C knock-in mice were viable and did not exhibit motor deficits up to 2 years of age. The mutant mice showed no significant differences in the number of Purkinje cells or motor neurons compared to wild-type littermates. Neuropathological examination revealed an absence of MATR3 and TDP-43 pathology in Purkinje cells and motor neurons in the mutant mice. Together, our results suggest that the F115C mutation in MATR3 may not confer pathogenicity.
MATR3 基因中的 F115C 突变与肌萎缩侧索硬化症（ALS）有关。为了确定 F115C 突变的致病性以及该突变导致 ALS 的机制，我们生成了在内源性鼠 Matr3 基因座中携带 F115C 突变的小鼠。杂合或纯合 MATR3 F115C 基因敲入小鼠具有活力，并且在 2 岁之前没有表现出运动缺陷。与野生型同窝仔相比，突变小鼠的浦肯野细胞或运动神经元数量没有明显差异。神经病理学检查显示突变小鼠的浦肯野细胞和运动神经元中不存在 MATR3 和 TDP-43 病理学。总之，我们的结果表明 MATR3 中的 F115C 突变可能不具有致病性。
