H. Manning
Faculty Member
Last active: 3/22/2018

Inducible loss of one Apc allele in Lrig1-expressing progenitor cells results in multiple distal colonic tumors with features of familial adenomatous polyposis.

Powell AE, Vlacich G, Zhao ZY, McKinley ET, Washington MK, Manning HC, Coffey RJ
Am J Physiol Gastrointest Liver Physiol. 2014 307 (1): G16-23

PMID: 24833705 · PMCID: PMC4080164 · DOI:10.1152/ajpgi.00358.2013

Individuals with familial adenomatous polyposis (FAP) harbor a germline mutation in adenomatous polyposis coli (APC). The major clinical manifestation is development of multiple colonic tumors at a young age due to stochastic loss of the remaining APC allele. Extracolonic features, including periampullary tumors, gastric abnormalities, and congenital hypertrophy of the retinal pigment epithelium, may occur. The objective of this study was to develop a mouse model that simulates these features of FAP. We combined our Lrig1-CreERT2/+ mice with Apcfl/+ mice, eliminated one copy of Apc in leucine-rich repeats and immunoglobulin-like domains protein 1 (Lrig1)-positive (Lrig1(+)) progenitor cells with tamoxifen injection, and monitored tumor formation in the colon by colonoscopy and PET. Initial loss of one Apc allele in Lrig1(+) cells results in a predictable pattern of preneoplastic changes, culminating in multiple distal colonic tumors within 50 days of induction, as well as the extracolonic manifestations of FAP mentioned above. We show that tumor formation can be monitored by noninvasive PET imaging. This inducible stem cell-driven model recapitulates features of FAP and offers a tractable platform on which therapeutic interventions can be monitored over time by colonoscopy and noninvasive imaging.

Copyright © 2014 the American Physiological Society.

MeSH Terms (17)

Adenomatous Polyposis Coli Animals Cell Transformation, Neoplastic Colon Colonoscopy Disease Models, Animal Genes, APC Hypertrophy Membrane Glycoproteins Mice Mice, Transgenic Neoplastic Stem Cells Nerve Tissue Proteins Positron-Emission Tomography Precancerous Conditions Retinal Pigment Epithelium Time Factors

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