Reference SummaryPowell AE, Am J Physiol Gastrointest Liver Physiol 2014 Jul 1;307(1):G16-23

Title

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

Authors

 Powell AE; Vlacich G; Zhao ZY; McKinley ET; Washington MK; Manning HC; Coffey RJ

Journal

 Am J Physiol Gastrointest Liver Physiol

Volume

 307

Issue

 1

Year

 2014

Pages

 G16-23

Abstract

 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.

Links

 J:221729 – MGI References
24833705 – National Library of Medicine/PubMed

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Eye - Retina lesion - epithelial
  • tamoxifen (for inducing expression from mutant alleles)
 Eye - Retina

observed
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Gastrointestinal tract tumor
  • tamoxifen (for inducing expression from mutant alleles)
 Gastrointestinal tract

observed
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Intestine - Large Intestine - Colon - Distal tumor
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine - Large Intestine - Colon - Distal

observed
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Intestine - Large Intestine - Colon - Distal tumor - luminal
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine - Large Intestine - Colon - Distal

observed
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Intestine - Large Intestine - Colon - Proximal tumor
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine - Large Intestine - Colon - Proximal

0
C57BL/6J-ApcMin/+ Intestine - Large Intestine - Colon adenoma - dysplastic
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine - Large Intestine - Colon

observed
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Intestine - Large Intestine - Colon adenoma - microadenoma
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine - Large Intestine - Colon

observed
C57BL/6J-ApcMin/+ Intestine - Large Intestine - Colon adenoma - tubular
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine - Large Intestine - Colon

observed
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Intestine - Large Intestine - Colon lesion
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine - Large Intestine - Colon

observed
C57BL/6J-ApcMin/+ Intestine - Large Intestine - Colon tumor
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine - Large Intestine - Colon

observed
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Intestine - Large Intestine - Colon tumor
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine - Large Intestine - Colon

observed
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Intestine - Small Intestine - Duodenum - Periampullary region adenoma
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine - Small Intestine - Duodenum - Periampullary region

80
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Intestine - Small Intestine - Duodenum - Periampullary region tumor
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine - Small Intestine - Duodenum - Periampullary region

80
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Intestine - Small Intestine - Duodenum tumor
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine - Small Intestine - Duodenum

observed
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Intestine - Small Intestine - Ileum tumor
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine - Small Intestine - Ileum

observed
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Intestine - Small Intestine - Jejunum tumor
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine - Small Intestine - Jejunum

observed
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Intestine - Small Intestine lesion
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine - Small Intestine

observed
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Intestine - Small Intestine tumor
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine - Small Intestine

observed
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Intestine dysplasia
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine

observed
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Intestine lesion
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine

observed
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Intestine neoplasia
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine

observed
C57BL/6J-ApcMin/+ Intestine tumor
  • tamoxifen (for inducing expression from mutant alleles)
 Intestine

observed
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Stomach - Fundus dysplasia
  • tamoxifen (for inducing expression from mutant alleles)
 Stomach - Fundus

observed
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Stomach - Fundus hyperplasia - foveolar
  • tamoxifen (for inducing expression from mutant alleles)
 Stomach - Fundus

observed
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Stomach - Fundus lesion - dysplastic
  • tamoxifen (for inducing expression from mutant alleles)
 Stomach - Fundus

observed
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Stomach - Glandular - Pyloric antrum dysplasia - high grade
  • tamoxifen (for inducing expression from mutant alleles)
 Stomach - Glandular - Pyloric antrum

observed - 100
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Stomach - Glandular - Pyloric antrum hyperplasia
  • tamoxifen (for inducing expression from mutant alleles)
 Stomach - Glandular - Pyloric antrum

observed
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Stomach - Glandular - Pyloric antrum lesion - dysplastic
  • tamoxifen (for inducing expression from mutant alleles)
 Stomach - Glandular - Pyloric antrum

observed
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Stomach - Glandular - Pylorus dysplasia - high grade
  • tamoxifen (for inducing expression from mutant alleles)
 Stomach - Glandular - Pylorus

100
[not specified]-Apctm2.1Cip/+ Lrig1tm1.1(cre/ERT2)Rjc/+ Stomach - Glandular - Pylorus lesion - dysplastic
  • tamoxifen (for inducing expression from mutant alleles)
 Stomach - Glandular - Pylorus

observed