More than two decades of Apc modeling in rodents

Abstract

Mutation of tumor suppressor gene Adenomatous polyposis coli (APC) is an initiating step in most colon cancers. This review summarizes Apc models in mice and rats, with particular concentration on those most recently developed, phenotypic variation among different models, and genotype/ phenotype correlations.

Multiple mucin depleted foci, high proliferation and low apoptotic response in the onset of colon carcinogenesis of the PIRC rat, mutated in Apc

“…5 As a matter of fact, despite the efforts to build new mouse models with more tumors in the colon, in the majority of the existing Apc-based models of colon cancer (e.g., Min mice), tumors develop mostly in the small intestine and only few arise in the colon. [2][3][4]22,23 This hinders the possibility to study the development of cancer in the very same organ in which the tumors arise in humans. [2][3][4] Colon carcinogenesis is a multistep process, starting from apparently normal crypts which transform into preneoplastic microscopic lesions which may eventually grow into larger adenomas and then malignant cancers.…”

“…1 Rodent models carrying mutations in Apc have been thus developed and widely used. 2,3 However, at variance with human pathology, the majority of these strains, including Apc Min (Min) mice, develops tumors predominantly in the small intestine and not in the colon. [2][3][4] This characteristic is a considerable drawback given the inherent diversity of these two parts of the intestine in terms of anatomy, lumen environment, physiology and propensity to tumor development.…”

“…2,3 However, at variance with human pathology, the majority of these strains, including Apc Min (Min) mice, develops tumors predominantly in the small intestine and not in the colon. [2][3][4] This characteristic is a considerable drawback given the inherent diversity of these two parts of the intestine in terms of anatomy, lumen environment, physiology and propensity to tumor development. [2][3][4] Few years ago, the PIRC rat (Polyposis In the Rat Colon) with a germline mutation in one allele of the Apc gene (F344/NTac-Apc am1137 ) has been described.…”

“…[2][3][4] This characteristic is a considerable drawback given the inherent diversity of these two parts of the intestine in terms of anatomy, lumen environment, physiology and propensity to tumor development. [2][3][4] Few years ago, the PIRC rat (Polyposis In the Rat Colon) with a germline mutation in one allele of the Apc gene (F344/NTac-Apc am1137 ) has been described. 5 Notably, at variance with pre-existing Apcbased mouse models, PIRC rats spontaneously develop tumors in the small intestine but also in the colon, thus mimicking more closely FAP and CRC and potentially standing for as a robust model of colon cancer.…”

“…10,11 Since Wnt-signaling activation is a hallmark of colon carcinogenesis, we also determined nuclear b-catenin in the MDF. [1][2][3] Finally, since altered proliferation, apoptosis and DNA damage/oxidative stress in the apparently NM could underlie the onset of tumorigenesis, we studied these processes in young PIRC rats (one-and two-month old) when only few MDF and no macroscopic tumors are present in the NM. 4,[12][13][14][15][16] …”