期刊
NATURE MEDICINE
卷 14, 期 9, 页码 979-984出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.1865
关键词
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资金
- Deutsche Forschungsgemeinschaft [FOR406]
- SFB [405 B10]
- US National Institutes of Health [R01-CA85610, R01-CA105102, 3R01CA089305-03S1]
- NIH/NCI ICMIC [P50, 1P20 CA112973]
- NATIONAL CANCER INSTITUTE [P01CA120964, R01CA105102, U56CA112973, R01CA085610, R01CA089305] Funding Source: NIH RePORTER
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.
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