1. Cre recombinase toxicity in podocytes: a novel genetic model for FSGS in adolescent mice
- Author
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Herdit Schueler, Bart Smeets, Katja Leuchtle, Arnaldo Chia-Gil, Henry B.P.M. Dijkman, Sonja Djudjaj, Kevin Schulte, Jürgen Floege, Madeleine A. Frahsek, and Marcus J. Moeller
- Subjects
Aging ,Pathology ,medicine.medical_specialty ,Physiology ,Transgene ,Cre recombinase ,Mice, Transgenic ,Biology ,urologic and male genital diseases ,Antibodies ,Gene Expression Regulation, Enzymologic ,Podocyte ,Mice ,All institutes and research themes of the Radboud University Medical Center ,Focal segmental glomerulosclerosis ,Genetic model ,medicine ,Animals ,Genetic Predisposition to Disease ,Doxycycline ,Integrases ,Glomerulosclerosis, Focal Segmental ,Podocytes ,medicine.disease ,female genital diseases and pregnancy complications ,Anti-Bacterial Agents ,Young age ,Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] ,medicine.anatomical_structure ,Toxicity ,medicine.drug - 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.
- Published
- 2019
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