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

Traykova-Brauch M, Schönig K, Greiner O, Miloud T, Jauch A, Bode M, Felsher DW, Glick AB, Kwiatkowski DJ, Bujard H, Horst J, von Knebel Doeberitz M, Niggli FK, Kriz W, Gröne HJ, Koesters R
Nat Med. 2008 14 (9): 979-84

PMID: 18724376 · PMCID: PMC3446847 · 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.

MeSH Terms (16)

Animals Disease Models, Animal Doxycycline Fibrosis Immunohistochemistry Kidney Tubules Mice Mice, Transgenic Paired Box Transcription Factors PAX8 Transcription Factor Polycystic Kidney Diseases Promoter Regions, Genetic Trans-Activators Transforming Growth Factor beta1 Tuberous Sclerosis Complex 1 Protein Tumor Suppressor Proteins

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