| Project/Area Number |
09558105
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Laboratory animal science
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
SERIKAWA Tadao Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (30025655)
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| Co-Investigator(Kenkyū-buntansha) |
KITADA Kazuhiro Kyoto University, Graduate School of Medicine, Instructor, 医学研究科, 助手 (70263093)
EJIMA Yohsuke Hiroshima Prefectural College of Health and Welfare, Department of Radiological Sciences and Technology, Professor, 放射線技術学科, 教授 (50127057)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥16,200,000 (Direct Cost: ¥16,200,000)
Fiscal Year 1999: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1998: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1997: ¥7,000,000 (Direct Cost: ¥7,000,000)
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| Keywords | Rat / Genetic linkage map / Comparative map / Disease model / mutant / genome / epilepsy / alymphoplasia / マイクロサテライト / 遺伝多型マーカー / 遺伝子連鎖地図 |
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| Research Abstract |
The rat has many unique features and advantages for understanding the biological and genetic bases of health and disease, and the great majority of rat models for human diseases are unique without known equivalents in other species. In this research project, we have improved the rat genetic map and rat-mouse-human comparative genome map to facilitate genetic analysis and positional cloning of causative genes in the rat models for human diseases. The resultant integrated rat map consists of 5,682 redundant markers, spanning a genetic length of 2,028 cM. Recently, a genome-wide rat-mouse-human comparative map based on newly developed radiation hybrid (RH) map of the rat genome has been reported. We have reported the 4th version of our comparative map based on mouse genetic map and its evaluation in respect of the completion. The total length of the conserved regions in the rat-mouse homologous map spans now 1199 cM (75%) on the mouse genetic map. In addition, we have identified the causative genes in mutant mouse and rat by positional cloning. 1) The alymphoplasia (aly) mutation of mouse is autosomal recessive and characterized by the systemic absence of lymph nodes and Peyer's pathches and disorganized splenic and thymic structures with immunode-ficiency. We found that the aly allele carries a point mutation causing an amino acid substitution in Nf-kb-inducing kinase (NIK). Transgenic complementation with wild-type Nik was successful. 2) The tremor rat exhibits absence-like seizures and spongiform degeneration in the central nervous system. By positional cloning, a genomic deletion was found within the critical region, in which aspartoacylase gene is located. Accordingly, no aspartoacylase activity was detected in any tissues examined and abnormal accumulation of N-acetyl-L-aspartate (NAA) was shown in the mutant brain. Interestingly, direct injection of NAA into normal rat cerebroventricule induced absence-like seizures similar to those seen in tremor rats.
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