International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany

Plenary Presentations * Oral Presentations *
Poster Presentations: Behavioural Genetics and Genomics * Development and Stem Cells * Functional Genome Analysis * Mouse Models of Human Disease * Mouse System Biology Bioinformatics * Multigenic and Multifactorial Trait Analysis * Nutrition and Metabolic Disease * Phenotyping Methods Imaging * The Genetics and Genomics of Infectious Disease *
Verne Chapman Memorial Lecture * Table of Contents * Sponsor/Exhibitor List * Awards * Photographs

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ORAL PRESENTATION

TUESDAY 11 NOVEMBER
11:30 – 11:45 HRS

FROM THE MIN MOUSE MODEL TO STUDIES OF THE INTESTINAL EPITHELIUM AND ITS NEOPLASMS IN THE MOUSE AND THE HUMAN

Dove W F
University of Wisconsin-Madison

Co-Authors: Chen X, Clipson L, Ehrhardt W, Haigis K, Halberg R, Hoff P, Kwong L, Newton M, Meyerand E, Pasch C, Shedlovsky A, Thliveris A, Weichert J, White A
Institutions: University of Wisconsin-Madison

One major pathway to colon cancer in mammals involves loss of function of the “gatekeeper gene” APC/Apc (Adenomatous polyposis coli). The Min nonsense allele of the murine Apc gene was induced by germline ENU mutagenesis, identified by its neoplastic phenotype, and cloned by a combination of low-resolution mapping and candidate testing. A single basepair change from the wildtype C57BL/6 Apc allele was detected, illustrating the power of the “coisogenic strategy” for positional cloning.

Our laboratory and others are studying a number of issues in the biology of intestinal neoplasia in the mouse, employing this Min model (Multiple intestinal neoplasia):

The different somatic genetic and epigenetic processes whereby the wildtype Apc function is lost in the early adenomas of Apc^Min/+ miceThe regional distribution of these distinct processes over the intestinal tractThe clonality of early neoplasmsThe modifiers of tumor formation, growth, and/or maintenance that are polymorophic in the mouse population

Cellular and molecular markers for the normal intestinal epithelium, its neoplasms, and the tumor-bearing host Imaging neoplastic growth and regression in vivo

Our final goal is to address how information from such studies of a series of mouse models can best be established as relevant (or not) to colon cancer in the human.