2001 Fiscal Year Final Research Report Summary
Cloning of causative gene responsible for a new ingerited cataract in the mouse
| Project/Area Number |
12680682
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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 |
Molecular biology
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| Research Institution | Tokyo Metropolitan Organization for Medical Science |
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Principal Investigator |
MAEDA Yukiko Y. The Tokyo Metropolitan Origannization of Medical Science, Tokyo Metropolitan Institute of Medical Science, Research associate, 東京都臨床医学総合研究所, 研究員 (40109947)
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| Co-Investigator(Kenkyū-buntansha) |
YONEKAWA Hiromichi The Tokyo Metropolitan Origannization of Medical Science, Tokyo Metropolitan Institute of Medical Science, Research associate, 東京都臨床医学総合研究所, 研究員 (30142110)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Mouse ingerited cataract, / Interval mapping of mouse genes, / Modifier gene / rct gene, / mrct gene, |
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| Research Abstract |
We discovered a new mutant mouse, RCT (Rinshoken Cataract), with a congenital cataract in strain SJL/J. Mouse models are effective tools to map human cataract genes to specific chromosomal region through conserved linkage between the human and the mouse, and consequently to elucidate the functions of their proteins. Our experimental results are : 1.Characteristics of RCT cataract. The opacity of the lens associated with microphthalmia could be observed visually at 3 to 3.5 months of age. Marked degeneration of the lens, including loss of the fine structure of the lens fibers and swelling of epithelial cells with vacuoles of various sizes in the cortex was detected. Histological changes in the lens were first observed at 2 days after birth. No sex-related differences were detected, and normal phenotypes in the F_<1> progeny of RCT and other normal strains. 2.Interval mapping. The chromosomal localization of causative gene was determined by interval mapping by using intersubspecific backcross progeny of RCT and MSM/Ms, an inbred strain from the Japanese wild mouse Mus musculus molossinus. Backcross progeny were divided into three groups according to phenotype : mice (1) with an early onset-cataract, which can be detected visually as in RCT mice, (2) with a late onset-cataract histologically but not visually, and (3) with normal lens. Allele combinations of two recessive genes, ret on chromosome 4 and mrct (a modifier of rct) on chromosome 5 regulated three phenotypes. 3.Gene isolation. To isolate ret gene, linkage analysis using more 1000 heads of (RCT x MSM/Ms) F_<2> mice was done, and BAC contig including the rct locus in the range of approximately 600 kbp was constructed almost. Six ESTs, which may be a candidate of rct gene, were found in the BAG contig.
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Research Products
(2 results)
