title: The utility of Apc-mutant rats in modeling human colon cancer.
abstract: Prior to the advent of genetic engineering in the mouse, the rat was the model of choice for investigating the etiology of cancer. Now, recent advances in the manipulation of the rat genome, combined with a growing recognition of the physiological differences between mice and rats, have reignited interest in the rat as a model of human cancer. Two recently developed rat models, the polyposis in the rat colon (Pirc) and Kyoto Apc Delta (KAD) strains, each carry mutations in the intestinal-cancer-associated adenomatous polyposis coli (Apc) gene. In contrast to mouse models carrying Apc mutations, in which cancers develop mainly in the small intestine rather than in the colon and there is no gender bias, these rat models exhibit colonic predisposition and gender-specific susceptibility, as seen in human colon cancer. The rat also provides other experimental resources as a model organism that are not provided by the mouse: the structure of its chromosomes facilitates the analysis of genomic events, the size of its colon permits longitudinal analysis of tumor growth, and the size of biological samples from the animal facilitates multiplexed molecular analyses of the tumor and its host. Thus, the underlying biology and experimental resources of these rat models provide important avenues for investigation. We anticipate that advances in disease modeling in the rat will synergize with resources that are being developed in the mouse to provide a deeper understanding of human colon cancer.
authors.affiliation: McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, Madison, WI 53792, USA.
authors.forename: Amy A
authors.initials: AA
authors.lastname: Irving
authors.affiliation: Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Yoshimi
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Hart
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Taybor
authors.initials: T
authors.lastname: Parker
authors.affiliation: McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, Madison, WI 53792, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Clipson
authors.affiliation: McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, Madison, WI 53792, USA.
authors.forename: Madeline R
authors.initials: MR
authors.lastname: Ford
authors.affiliation: Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kuramoto
authors.affiliation: McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, Madison, WI 53792, USA.
authors.forename: William F
authors.initials: WF
authors.lastname: Dove
authors.affiliation: McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, Madison, WI 53792, USA. Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA. amoslandgrafj@missouri.edu.
authors.forename: James M
authors.initials: JM
authors.lastname: Amos-Landgraf
mesh_terms: D000818:Animals; D006801:Humans; D051381:Rats; D003110:Colonic Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D042241:Early Diagnosis; D005838:Genotype; D009154:Mutation; D010641:Phenotype
keywords: APC; Allelic series; Animal models; Colorectal cancer