The Min (multiple intestinal neoplasia) mutation: its effect on gut epithelial cell differentiation and interaction with a modifier system
| Autor: | Kevin A. Roth, J I Gordon, A R Moser, W F Dove |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1992 |
| Předmět: |
Adenoma
Serotonin Cellular differentiation Enteroendocrine cell Mice Inbred Strains Nerve Tissue Proteins Biology medicine.disease_cause Fatty Acid-Binding Proteins Epithelium Mice Intestinal Neoplasms medicine Animals Intestinal Mucosa Crosses Genetic Epithelial cell differentiation Fatty Acids Mucins Cell Differentiation Cell Biology Articles medicine.disease Molecular biology Mice Mutant Strains Gut Epithelium Neoplasm Proteins medicine.anatomical_structure Phenotype Multipotent Stem Cell Immunology Mutation Neoplastic Stem Cells Muramidase Carcinogenesis Carrier Proteins Fatty Acid-Binding Protein 7 |
| Zdroj: | The Journal of Cell Biology Scopus-Elsevier |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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