1998 Fiscal Year Final Research Report Summary
Mapping of modifier loci affecting Min-induced intestinal neoplasia in Mice
| Project/Area Number |
08670269
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | The Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
OKAMOTO Mieko The Tokyo Metropolitan Institute of Medical Science, Department of Laboratory Animal Science, Researcher, 実験動物研究部門, 研究員 (80152354)
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| Project Period (FY) |
1996 – 1998
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| Keywords | Min mouse / intestinal neoplasia / Moml(Modifier of Min-1) / QTL mapping / modifier gene |
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| Research Abstract |
The Multiple intestinal neoplasia (Min) mouse, which carries a nonsense mutation in one Apc allele, develops many intestinal adenomas. The severity of neoplastic phenotype is strongly dependent on its genetic background. We found that the genetic background of an inbred strain derived from Japanese wild mouse could almost completely suppress Min-induced tumor formation. Linkage analysis of backcross mice with microsatellite markers, revealed that a considerable part of the suppressive effect is attributable to the known modifier Mom1 on chromosome 4. Beyond Mom1, several other modifier loci seemed to exist in the wild mouse-derived genetic background. In order to identify these modifiers , linkage disequilibrium analysis was carried out using a total of 138 microsatellite markers on 124 N2 segregants of extreme tumor phenotypes. Several candidate modifier loci are mapped on chromosomes 1, 3, 5, 7, 8,9, 11, 14, and 18. Some of the loci exert to reduce the severity of Min-induced phenotype, and the others, to increase it. We are now attempting to generate congenic lines in which candidate chromosomal regions of wild mouse is carried on the parental B6 genetic background.
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