Apc deficiency predisposes to renal carcinoma in the mouse.
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 beta-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.
Sansom
Owen J
OJ
Cardiff School of Biosciences, Cardiff University, Wales CF10 3US, UK.
Griffiths
David F R
DF
Reed
Karen R
KR
Winton
Douglas J
DJ
Clarke
Alan R
AR
D000818:Animals; D017353:Gene Deletion; D017491:Genes, APC; D006720:Homozygote; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D007680:Kidney Neoplasms / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics; D019459:Urothelium / Q000473:pathology / Q000502:physiology
D016159:Tumor Suppressor Protein p53; C045073:Cre recombinase; D019426:Integrases