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Apc deficiency predisposes to renal carcinoma in the mouse

Abstract

Deregulation of Wnt signalling has recently been implicated in human renal cancer. Here, we directly test this association by using a Cre-LoxP strategy to inactivate the Adenomatous Polyposis Coli (Apc) gene in the murine renal epithelium. Mice homozygous for a conditional Apc allele were intercrossed with mice transgenic for Cre recombinase under control of the Cyp1A promoter, which delivers constitutive recombination within a proportion of cells in the renal epithelium. Inactivation of Apc leads to the accumulation of nuclear β-catenin and the rapid development of multiple dysplastic foci. Renal carcinoma was observed with an earliest onset of 4 months. This predisposition was accelerated by p53 deficiency, reducing the earliest onset to 2 months. Compared to other murine models of kidney neoplasia, this represents particularly rapid onset of disease, and so implicates an important role for Apc in suppressing renal carcinoma.

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Acknowledgements

We thank Mark Bishop for technical assistance. This work was supported by the Wales Gene Park and grants from CR-UK and the BBSRC.

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Correspondence to Alan R Clarke.

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Supplementary Information accompanies the paper on oncogene website (http://www.nature.com/onc)

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Sansom, O., Griffiths, D., Reed, K. et al. Apc deficiency predisposes to renal carcinoma in the mouse. Oncogene 24, 8205–8210 (2005). https://doi.org/10.1038/sj.onc.1208956

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Keywords

  • Apc
  • kidney
  • Wnt
  • Cre
  • renal cancer

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