Role of Bim and apoptosis in the development of polycystic kidney disease (PKD) (C03)

缺乏生存因子Bcl-2的小鼠会发生多囊肾病（PKD），该疾病是通过促凋亡的仅bh3蛋白Bim介导的，但细胞凋亡如何导致该疾病尚不清楚。此外，目前尚不清楚其他仅bh3蛋白如Puma是否参与这一过程，以及细胞凋亡是否也是由多囊蛋白-1基因Pkd1突变引起的人类缓慢进展的晚发性常染色体显性多囊肾病（ADPKD）出现的关键。在这个提议中，我们将使用缺乏Bci-2或Pkd1（肾脏特异性或诱导）的小鼠和这些小鼠的分离肾细胞来确定Bim和/或Puma是否以及如何促进膀胱形成和PKD。

Mice deficient of the survival factor Bcl-2 develop polycystic kidney disease (PKD) that is mediated via the pro-apoptotic BH3-only protein Bim, but how apoptosis contributes to the disease is unknown. Moreover, it has been unclear if other BH3-only proteins such as Puma participate in the process and if apoptosis is also crucial for the emergence of the slowly progressing, late-onset autosomal dominant polycystic kidney disease (ADPKD) in humans caused by mutations in the polycystin-1 gene Pkd1. In this proposal we will use mice lacking Bci-2 or Pkd1 (kidney specific or induced) and isolated kidney cells of these mice to determine if and how Bim and/or Puma contribute to cystogenesis and PKD.