Transgenic Mice Expressing Mutant Protein Kinase C lota in the Colonic Epithelium

Reference #:

2003-222

Inventors/Contributors

Alan P. Fields, Ph.D., Lee Jamieson, Nicole R. Murray, Ph.D., Melody L. Stallings-Mann, Ph.D.

Description

These mice represent a model for colon cancer progression from adenoma to carcinoma. C57BI/6J mice were engineered to express either constitutively active (ca) or inase-deficient (kd) protein kinase C iota (PKCiota) in the colonic epithelium. Although these mice have been characterized to have little to no change in colonic epithelial cell homeostasis, they have been found to be significantly more (caPKCiota) or less (kdPKCiota) susceptible to carcinogen-induced colon cancer. caPKCiota mice develop predominantly adenocarcinoma whereas wild-type mice develop predominantly adenomas. In addition, expression of kdPKCiota renders mice less susceptible to oncogenic Kras-induced colon carcinogenesis. These mice demonstrate that PKCiota is an attractive target for chemotherapeutic development and represent an important pre-clinical model that will be useful for evaluating novel therapeutics for the treatment of colon cancer.

Patent Status

Pending