Apc mice: models, modifiers and mutants.
The mouse provides an excellent in vivo system with which to model human diseases and to test therapies. Mutations in the Adenomatous polyposis coli (APC) gene are required to initiate familial adenomatous polyposis (FAP) and are also important in sporadic colorectal cancer tumorigenesis. The (multiple intestinal neoplasia Min) mouse contains a point mutation in the Apc gene, develops numerous adenomas and was the first model used to study the involvement of the Apc gene in intestinal tumorigenesis. The model has provided examples of modifying loci (called Modifiers of Min: Mom) in mice, demonstrating the principle of genetic modulation of disease severity. A spectrum of Apc mutant mice has since been developed, each with defining characteristics, some more able to accurately model human polyposis and colon cancer. We will focus our review on Apc mutant mouse models, the advent of models with concurrent or compound mutations and the importance of genetic background when modeling polyposis and cancer. Brief consideration will be given to the use of these models in drug testing.
McCart
Amy E
AE
Colorectal Cancer Genetics Group, Institute of Cell and Molecular Science, Barts and The London, Queen Mary's School of Medicine and Dentistry, 4 Newark Street, Whitechapel, London E1 2AT, UK.
Vickaryous
Nicola K
NK
Silver
Andrew
A
D011125:Adenomatous Polyposis Coli / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000818:Animals; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC; D042822:Genomic Instability; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains