Mouse models of gastrointestinal tumors

Abstract

The laboratory mouse (Mus musculus) has become one of the best model animal species in biomedical research today because of its abundant genetic/genomic information, and easy mutagenesis using transgenic and gene knockout technology. Genetically engineered mice have become essential tools in both mechanistic studies and drug development. In this article I will review recent topics in gastrointestinal cancer model mice, with emphasis on the results obtained in our laboratory. They include: (i) mouse models for familial adenomatous polyposis (Apc mutant mice; modifier genes of Apc intestinal polyposis; stabilizing beta-catenin mutant mice); (ii) mouse models for colon cancer (mouse models for hereditary non-polyposis colon cancer; additional mutations in Apc mutant mice; models with mutations in other genes; models for colon cancer associated with inflammatory bowel diseases); and (iii) mouse models for gastric cancer.

Figure 1

Schematic presentation of the canonical Wnt signal pathway. The left side shows the normal adult tissues where phosphorylation of β‐catenin target serine/threonine residues are phosphorylated and degraded rapidly by ubiquitination. The right side indicates the transcriptional activation of the Wnt target genes by unphosphorylated and therefore stabilized β‐catenin. APC, adenomatous polyposis coli.

Figure 2

Schematic presentation of arachidonic acid metabolism in the context of intestinal polyposis. COX, cyclooxygenase; PG, prostaglandin; TX, thromboxane.

Figure 3

A likely mechanism for hyperplastic tumor development by Helicobacter pylori infection. COX, cyclooxygenase; GF, growth factor; PG, prostaglandin; TNF‐α, tumour necrosis factor‐α.