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Diabetes accelerates cystogenesis in the adult conditional ift88 knockout mouse
Author(s) -
Sas Kelli Margot,
Amria May Y.,
Bell P. Darwin
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.664.9
Subject(s) - cilium , diabetes mellitus , kidney , endocrinology , medicine , muscle hypertrophy , conditional gene knockout , streptozotocin , biology , microbiology and biotechnology , gene , phenotype , biochemistry
Recently we found that deletion of cilia in the adult mouse exacerbates renal hypertrophy and accelerates cystogenesis in response to unilateral nephrectomy. Diabetes, the leading cause of end stage renal disease, also results in structural and functional hypertrophy in the kidney. The goal of this study was to determine if the presence of diabetes would modify the time course of cyst formation in the adult mouse with deletion of cilia. To examine the role of cilia in diabetes, we utilized a conditional floxed allele for the ift88/Tg737 gene to produce cilia (+) or cilia (−) adult mice. Mice were administered streptozotocin at 50 mg/kg for 5 days to induce diabetes. Blood glucose concentrations were elevated but not significantly different between groups. After 6 weeks, mice underwent MRI to determine cystic burden and kidneys were removed after 12 weeks for histological analysis. MRI and histological analyses identified accelerated cystogenesis mainly in the glomeruli and collecting ducts of diabetic cilia (−) mice, as well as exaggerated structural hypertrophy. There was also a marked increase in lymphocytic infiltration as well as interstitial inflammation. Additionally, there was enhanced mTOR activity in kidneys from the diabetic cilia (−) mice. Thus diabetes may be a significant risk factor for accelerated cyst formation and renal failure in PKD. This work was supported by NIH grants and a VA Merit Award.