Complete deletion of Apc results in severe polyposis in mice

Oncogene. 2010 Mar 25;29(12):1857-64. doi: 10.1038/onc.2009.457. Epub 2009 Dec 14.


The adenomatous polyposis coli (APC) gene product is mutated in the vast majority of human colorectal cancers. APC negatively regulates the WNT pathway by aiding in the degradation of beta-catenin, which is the transcription factor activated downstream of WNT signaling. APC mutations result in beta-catenin stabilization and constitutive WNT pathway activation, leading to aberrant cellular proliferation. APC mutations associated with colorectal cancer commonly fall in a region of the gene termed the mutation cluster region and result in expression of an N-terminal fragment of the APC protein. Biochemical and molecular studies have revealed localization of APC/Apc to different sub-cellular compartments and various proteins outside of the WNT pathway that associate with truncated APC/Apc. These observations and genotype-phenotype correlations have led to the suggestion that truncated APC bears neomorphic and/or dominant-negative function that support tumor development. To analyze this possibility, we have generated a novel allele of Apc in the mouse that yields complete loss of Apc protein. Our studies reveal that whole-gene deletion of Apc results in more rapid tumor development than the APC multiple intestinal neoplasia (Apc(Min)) truncation. Furthermore, we found that adenomas bearing truncated Apc had increased beta-catenin activity when compared with tumors lacking Apc protein, which could lead to context-dependent inhibition of tumorigenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli / genetics*
  • Adenomatous Polyposis Coli / prevention & control
  • Animals
  • Codon / genetics
  • Codon, Nonsense
  • Disease Models, Animal
  • Gene Deletion*
  • Genes, APC*
  • Genetic Carrier Screening
  • Genotype
  • Humans
  • Intestinal Neoplasms / genetics
  • Mice
  • Mice, Inbred C57BL / genetics
  • Multigene Family / genetics
  • Mutation
  • Phenotype
  • beta Catenin / metabolism


  • Codon
  • Codon, Nonsense
  • beta Catenin