Disruption of Tubular Flcn Expression as a Mouse Model for Renal Tumor Induction

    November 2015 in “ Kidney International ”
    Jindong Chen, Dachuan Huang, Isabelle Rubera, Kitaro Futami, Pengfei Wang, Peter Zlckert, Sok Kean Khoo, Karl Dykema, Ping Zhao, David Petillo, Brian Cao, Zhongfa Zhang, Shuhui Si, Susan R. Schoen, Ximing J. Yang, Ming Zhou, Guang-Qian Xiao, Guan Wu, Magnus Nordenskjöld, Michel Tauc, Bart O. Williams, Kyle A. Furge, Bin Tean Teh
    TLDR Disrupting the Flcn gene in mice causes early kidney cysts and tumors, which can be treated with rapamycin.
    The study developed a kidney-specific knockout mouse model by disrupting the Flcn gene in proximal tubules, resulting in early-onset renal cysts and multiple histological subtypes of renal neoplasms with high tumor penetrance. Chromophobe renal cell carcinomas were predominant in younger mice, while papillary renal cell carcinomas were more common in older mice. The progression from cystic hyperplasia to high-grade tumors was observed, with upregulated mTOR and TGF-β signaling pathways. Treatment with the mTOR inhibitor rapamycin suppressed tumor growth. Out of 100 knockout mice, 53 developed kidney tumors, and all had cysts, leading to death within 2 years due to kidney failure. This model provided a more accurate representation of human Birt-Hogg-Dubé syndrome kidney tumorigenesis and extended lifespan compared to previous models, making it suitable for preclinical applications.
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