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Am J Physiol Renal Physiol ; 317(5): F1375-F1382, 2019 11 01.
Article in English | MEDLINE | ID: mdl-31588799

ABSTRACT

Here, we show that inducible overexpression of Cre recombinase in glomerular podocytes but not in parietal epithelial cells may trigger focal segmental glomerulosclerosis (FSGS) in juvenile transgenic homocygous Pod-rtTA/LC1 mice. Administration of doxycycline shortly after birth, but not at any other time point later in life, resulted in podocyte injury and development of classical FSGS lesions in these mice. Sclerotic lesions were formed as soon as 3 wk of age, and FSGS progressed with low variability until 13 wk of age. In addition, our experiments identified Cre toxicity as a potentially relevant limitation for studies in podocytes of transgenic animals. In summary, our study establishes a novel genetic model for FSGS in mice, which exhibits low variability and manifests already at a young age.


Subject(s)
Aging , Genetic Predisposition to Disease , Glomerulosclerosis, Focal Segmental/genetics , Integrases/metabolism , Podocytes/metabolism , Animals , Anti-Bacterial Agents/pharmacology , Antibodies , Doxycycline/pharmacology , Gene Expression Regulation, Enzymologic/drug effects , Gene Expression Regulation, Enzymologic/genetics , Integrases/genetics , Mice , Mice, Transgenic
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