Generation of an inducible colon-specific Cre enzyme mouse line for colon cancer research

Significance A major limitation of current mouse models of colorectal cancer (CRC) is that the cancer that develops is often significantly different from human colon cancer in terms of latency, intestinal location, or molecular signature. Carbonic anhydrase I ( Car1 ) is a gene expressed by colonic epithelial cells. We generated an inducible Car1 CreER mouse model with Cre expression in the cecum and proximal colon. Mutations of genes that drive human CRC with our Car1 CreER mouse yielded tumors exclusively in the cecum and proximal colon. Differentiated colonic cells in the proximal colon with Apc/Kras mutations initiate tumors supporting a top-down model of intestinal tumorigenesis. The inducible Car1 CreER will be a useful model in studying human intestinal cancers originating from the proximal colon.