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Updated: Aug 7, 2026
Modeling Spontaneous Metastatic Renal Cell Carcinoma (mRCC) in Mice Following Nephrectomy
Published on: April 29, 2014
Apc deficiency predisposes to renal carcinoma in the mouse
Owen J Sansom1, David F R Griffiths, Karen R Reed
1Cardiff School of Biosciences, Cardiff University, Wales CF10 3US, UK.
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 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.
Insights
The Adenomatous Polyposis Coli (Apc) gene is crucial for suppressing kidney cancer. Inactivating Apc in mice led to rapid renal carcinoma development, highlighting its tumor-suppressive role.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Wnt signaling pathway deregulation is linked to human renal cancer.
- The Adenomatous Polyposis Coli (Apc) gene plays a role in Wnt pathway regulation.
Purpose of the Study:
- To investigate the direct association between Apc gene inactivation and renal cancer development.
- To establish a murine model for studying Apc's role in renal tumorigenesis.
Main Methods:
- Utilized a Cre-LoxP strategy to conditionally inactivate the Apc gene in murine renal epithelium.
- Generated mice with conditional Apc alleles crossed with Cre recombinase transgenic mice (Cyp1A promoter).
Main Results:
- Apc inactivation resulted in nuclear beta-catenin accumulation and rapid development of dysplastic foci.
- Renal carcinoma onset observed as early as 4 months in Apc-deficient mice.
- p53 deficiency accelerated renal carcinoma onset to 2 months.
Conclusions:
- Apc is a critical suppressor of renal carcinoma in mice.
- This model demonstrates a particularly rapid onset of kidney neoplasia, underscoring Apc's importance.
