Biochemical and neuropathological analysis of HtrA2 knockout mouse

我们产生了HtrA 2敲除（KO）小鼠，并对它们进行了生化和神经病理学分析。我们发现纯合HtrA2 KO小鼠的平均存活期为30天。在小鼠中，纹状体退化，泛素化蛋白积聚。此外，我们发现COXI、COXIV和parkin蛋白减少，而LC 3-II增加。他们的骨骼肌和心肌出现萎缩。HtrA2/parkin双基因敲除小鼠的平均生存期短于HtrA2基因敲除小鼠。此外，我们确定了HtrA2免疫反应性的老年斑和神经元缠结的阿尔茨海默氏症和肌萎缩侧索硬化症患者的胞浆内包涵体。

We generated HtrA2 knockout(KO) mice, and analyzed them biochemically and neuropathologically. We found that the mean survival of the homozygous HtrA2 KO mice was 30 days. In the mice, the striatum was degenerated and ubiquitinated proteins were accumulated. In addition, we found reduction of COXI, COXIV, and parkin proteins, and increase of LC3-II. Their skeletal and cardiac muscles showed atrophy. The mean survival of HtrA2/parkin double KO mice was shorter than that of HtrA2 KO mice. Moreover, we identified HtrA2 immunoreactivity in the senile plaques and the neurofibrillary tangles of Alzheimer's and in the intracytoplasmic inclusions of ALS patients.