The Journal of Cell Biology, Vol 116, 1517-1526, Copyright © 1992 by The Rockefeller University Press

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

AR Moser, WF Dove, KA Roth and JI Gordon
McArdle Laboratory, University of Wisconsin, Madison 53706.

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.
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• Tsao, J.-L., Zhang, J., Salovaara, R., Li, Z.-H., Jarvinen, H. J., Mecklin, J.-P., Aaltonen, L. A., Shibata, D. (1998). Tracing Cell Fates in Human Colorectal Tumors from Somatic Microsatellite Mutations : Evidence of Adenomas with Stem Cell Architecture. Am. J. Pathol. 153: 1189-1200 [Abstract] [Full Text]  
• Shoemaker, A. R., Moser, A. R., Midgley, C. A., Clipson, L., Newton, M. A., Dove, W. F. (1998). A resistant genetic background leading to incomplete penetrance of intestinal neoplasia and reduced loss of heterozygosity in ApcMin/+ mice. Proc. Natl. Acad. Sci. USA 95: 10826-10831 [Abstract] [Full Text]  
• Kalitsis, P., Fowler, K. J., Earle, E., Hill, J., Choo, K. H. A. (1998). Targeted disruption of mouse centromere protein C gene leads to mitotic disarray and early embryo death. Proc. Natl. Acad. Sci. USA 95: 1136-1141 [Abstract] [Full Text]  
• Fazeli, A., Steen, R. G., Dickinson, S. L., Bautista, D., Dietrich, W. F., Bronson, R. T., Bresalier, R. S., Lander, E. S., Costa, J., Weinberg, R. A. (1997). Effects of p53 mutations on apoptosis in mouse intestinal and human colonic adenomas. Proc. Natl. Acad. Sci. USA 94: 10199-10204 [Abstract] [Full Text]  
• Coopersmith, C. M., Chandrasekaran, C., McNevin, M. S., Gordon, J. I. (1997). Bi-transgenic Mice Reveal that K-rasVal12 Augments a p53-independent Apoptosis When Small Intestinal Villus Enterocytes Reenter the Cell Cycle. JCB 138: 167-179 [Abstract] [Full Text]  
• Gould, K. A., Dove, W. F. (1997). Localized gene action controlling intestinal neoplasia in mice. Proc. Natl. Acad. Sci. USA 94: 5848-5853 [Abstract] [Full Text]  
• Thompson, M.B. (1997). The Min Mouse: A Genetic Model for Intestinal Carcinogenesis. Toxicol Pathol 25: 329-332  
• Wasan, H. S., Novelli, M., Bee, J., Bodmer, W. F. (1997). Dietary fat influences on polyp phenotype in multiple intestinal neoplasia mice. Proc. Natl. Acad. Sci. USA 94: 3308-3313 [Abstract] [Full Text]  
• King, D.P., Takahashi, J.S. (1996). Forward Genetic Approaches to Circadian Clocks in Mice. Cold Spring Harb Symp Quant Biol 61: 295-302 [Abstract]  
• Hermiston, M. L., Gordon, J. I. (1995). Inflammatory Bowel Disease and Adenomas in Mice Expressing a Dominant Negative N-Cadherin. Science 270: 1203-1207 [Abstract]  
• Baribault, H, Penner, J, Iozzo, R V, Wilson-Heiner, M (1994). Colorectal hyperplasia and inflammation in keratin 8-deficient FVB/N mice.. Genes Dev. 8: 2964-2973 [Abstract]  
• Dove, W.F., Luongo, C., Connelly, C.S., Gould, K.A., Shoemaker, A.R., Moser, A.R., Gardner, R.L. (1994). The Adenomatous Polyposis Coli Gene of the Mouse in Development and Neoplasia. Cold Spring Harb Symp Quant Biol 59: 501-508 [Abstract]  
• Pories, S. E., Ramchurren, N., Summerhayes, I., Steele, G. (1993). Animal Models for Colon Carcinogenesis. Arch Surg 128: 647-653 [Abstract]  
• Su, L., Kinzler, K., Vogelstein, B, Preisinger, A., Moser, A., Luongo, C, Gould, K., Dove, W. (1992). Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science 256: 668-670 [Abstract]  
• Hong, K. H., Bonventre, J. C., O'Leary, E., Bonventre, J. V., Lander, E. S. (2001). Deletion of cytosolic phospholipase A2 suppresses ApcMin-induced tumorigenesis. Proc. Natl. Acad. Sci. USA 98: 3935-3939 [Abstract] [Full Text]  

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