An efficient and versatile system for acute and chronic modulation of renal tubular function in transgenic mice

作者：Traykova Brauch Milena; Schoenig Kai; Greiner Oliver; Miloud Tewfik; Jauch Anna; Bode Manja; Felsher Dean W; Glick Adam B; Kwiatkowski David J; Bujard Hermann; Horst Juergen; Doeberitz Magnus von Knebel; Niggli Felix K; Kriz Wilhelm; Groene Hermann Josef; Koesters Robert^*

来源：Nature Medicine, 2008, 14(9): 979-984.

DOI：10.1038/nm.1865

We describe a transgenic mouse line, Pax8-rtTA, which, under control of the mouse Pax8 promoter, directs high levels of expression of the reverse tetracycline-dependent transactivator (rtTA) to all proximal and distal tubules and the entire collecting duct system of both embryonic and adult kidneys. Using crosses of Pax8-rtTA mice with tetracycline-responsive c-MYC mice, we established a new, inducible model of polycystic kidney disease that can mimic adult onset and that shows progression to renal malignant disease. When targeting the expression of transforming growth factor-beta 1 to the kidney, we avoided early lethality by discontinuous treatment and successfully established an inducible model of renal fibrosis. Finally, a conditional knockout of the gene encoding tuberous sclerosis complex-1 was achieved, which resulted in the early outgrowth of giant polycystic kidneys reminiscent of autosomal recessive polycystic kidney disease. These experiments establish Pax8-rtTA mice as a powerful tool for modeling renal diseases in transgenic mice.

• 出版日期2008-9
• 单位上海市精神卫生中心