Reference SummaryMoser AR, J Cell Biol 1992 Mar;116(6):1517-26

Title

The Min (multiple intestinal neoplasia) mutation: its effect on gut epithelial cell differentiation and interaction with a modifier system.

Authors

Moser AR; Dove WF; Roth KA; Gordon JI

Journal

J Cell Biol

Volume

116

Issue

6

Year

1992

Pages

1517-26

Abstract

Min is a fully penetrant dominant mutation that leads to the development of multiple intestinal adenomas throughout the duodenal-to-colonic axis. Min/+ C57BL6/J mice have an average life-span of 120 d. Multi-label immunocytochemical studies of these lesions demonstrate patches of differentiated enterocytes, and scattered enteroendocrine, goblet and Paneth cells. Expression of endogenous marker genes within these differentiated cells can be directly correlated with the position occupied by the adenoma along the duodenal-to-colonic axis and mirrors the regional differentiation of the normal gut epithelium. The presence of multiple lineages in adenomas together with their retention of spatial information suggests that tumorigenesis in Min/+ mice may be initiated in a multipotent stem cell normally located at the base of intestinal crypts. To study the time-dependent properties of these tumors, genetic conditions were sought in which Min/+ animals could survive for up to 300 d. Min is fully penetrant in hybrids with either AKR/J or MA/MyJ. However, the hybrids demonstrate a reduction in the number of intestinal adenomas. Preliminary backcross analysis is consistent with a single major modifier locus unlinked to Min in both the AKR/J and MA/MyJ strains. The increased lifespan of the hybrid animals is also associated with the development of invasive tumors. New tumors do not arise continuously over the lifespan of these animals; instead all adenomas appear to be established by 100 d of age or sooner. These studies indicate that the Min/+ mouse is a powerful model system for analyzing the mechanisms that establish and maintain a balance between proliferation and differentiation in the continuously renewing gut epithelium and for an assessment of the multi-step hypothesis of intestinal neoplasia.

Links

J:1879 – Mouse Genome Informatics
1541640 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
C57BL/6J-ApcMin/+ Intestine - Large Intestine - Colon - Distal adenoma Intestine - Large Intestine - Colon - Distal

observed

C57BL/6J-ApcMin/+ Intestine - Large Intestine - Colon - Proximal adenoma Intestine - Large Intestine - Colon - Proximal

observed

C57BL/6J-ApcMin/+ Intestine - Large Intestine - Colon adenoma Intestine - Large Intestine - Colon

observed

MAB6F1-ApcMin/+ Intestine - Large Intestine - Colon adenoma Intestine - Large Intestine - Colon

observed

AKB6F1-ApcMin/+ Intestine - Large Intestine - Colon adenoma Intestine - Large Intestine - Colon

observed

C57BL/6J-ApcMin/+ Intestine - Large Intestine adenoma Intestine - Large Intestine

observed

C57BL/6J-ApcMin/+ Intestine - Small Intestine - Duodenum adenoma Intestine - Small Intestine - Duodenum

observed

C57BL/6J-ApcMin/+ Intestine - Small Intestine - Ileum adenoma Intestine - Small Intestine - Ileum

observed

(AKMAF1 x C57BL/6J)-ApcMin/+ Intestine - Small Intestine - Jejunum adenocarcinoma Intestine - Small Intestine - Jejunum

observed

C57BL/6J-ApcMin/+ Intestine - Small Intestine - Jejunum adenoma Intestine - Small Intestine - Jejunum

observed

(AKMAF1 x C57BL/6J)-ApcMin/+ Intestine - Small Intestine adenocarcinoma Intestine - Small Intestine

observed

C57BL/6J-ApcMin/+ Intestine - Small Intestine adenoma Intestine - Small Intestine

observed

MAB6F1-ApcMin/+ Intestine - Small Intestine adenoma Intestine - Small Intestine

observed

AKB6F1-ApcMin/+ Intestine - Small Intestine adenoma Intestine - Small Intestine

observed

C57BL/6J-ApcMin/+ Intestine adenocarcinoma Intestine

0

C57BL/6J-ApcMin/+ Intestine adenoma Intestine

43

MAB6F1-ApcMin/+ Intestine adenoma Intestine

64

AKB6F1-ApcMin/+ Intestine adenoma Intestine

46 - 57

MA;B6-ApcMin/+ Intestine adenoma Intestine

observed

AK;B6-ApcMin/+ Intestine adenoma Intestine

observed