Cre recombinase toxicity in podocytes: a novel genetic model for FSGS in adolescent mice

Am J Physiol Renal Physiol. 2019 Nov 1;317(5):F1375-F1382. doi: 10.1152/ajprenal.00573.2018. Epub 2019 Oct 7.


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.

Keywords: chronic kidney disease; focal segmental glomerulosclerosis; podocyte; transgenic mouse model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Anti-Bacterial Agents
  • Antibodies
  • Cre recombinase
  • Integrases
  • Doxycycline