International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)

Table of Contents * Genes, Physical Mapping and Sequencing * Gene Identification * Bioinformatics * Common Resources * RIKEN Session * Functional Genomics * Complex Traits * Mutagenesis * Developmental Genetics and Differentiation * Verne Chapman Memorial Lecture I and II

I19. Genetic Interaction of the Apc<min> and the Egfr<wa2> Alleles

Reade B. Roberts, David W. Threadgill
Dept. of Genetics, University of North Carolina, Chapel Hill, NC 27599-7264

Numerous studies have circumstantially linked the epidermal growth factor receptor (Egfr) to the initiation and progression of colorectal cancer. Misregulation of Egfr would allow the receptor to disrupt various cell functions including adhesion, apoptosis, cell growth, and cell proliferation. Crossing the Apc<min> mouse model of intestinal polyposis onto the kinase-impaired Egfr<wa2> background results in a 10-fold reduction in polyp number relative to Apc<min> mice carrying a wild-type Egfr allele. Interestingly, no significant difference in mean polyp size is observed between these two classes of mice. Histological analysis reveals no obvious differences between Apc<min> polyps developing on the Egfr<wa2> and wild-type Egfr backgrounds. These initial results suggest a requirement for Egfr in the initiation of Apc<min> tumorigenesis, but not in progression. Thus, wild-type Egfr activity is required for polyp formation; polyps forming on an Egfr<wa2> background may escape this requirement by perturbation of other signaling pathways.

We are currently investigating the mechanism underlying the genetic interaction of Apc<min> and Egfr<wa2>. Further studies to determine whether ectopic Egfr activation is sufficient to enhance Apc<min> tumorigenesis are also underway. The results of these studies will also be presented.