| Project/Area Number |
16300140
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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 | 一般 |
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| Research Field |
Laboratory animal science
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| Research Institution | RIKEN |
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Principal Investigator |
ABE Kuniya RIKEN BioResource Center, Technology and Development Team for Mammalian Cellular Dynamics, Head, 動物変異動態解析技術開発チーム, チームリーダー (40240915)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIMOTO Michihiko RIKEN BioResource Center, Technology and Development Team for Mammalian Cellular Dynamics, Research & Development Scientist, 動物変異動態解析技術開発チーム, 開発研究員 (10373317)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2006: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2005: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2004: ¥6,200,000 (Direct Cost: ¥6,200,000)
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| Keywords | BAC / Japanese mouse subspecies / transgenic mouse / SNP / Functional genomics / マウス遺伝学 / 近交系マウス / BACライブラリー / 相同組換え / 日本固有マウス亜種 / ゲノム進化 / 亜種分化 |
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| Research Abstract |
MSM/Ms is an inbred strain derived from the Japanese wild mouse, Mus musculus molossinus. In order to gain genomic information from MSM/Ms, we constructed an arrayed bacterial artificial chromosome (BAC) library from male MSM/Ms genomic DNA, covering genome equivalent. Both ends of 176,256 BAC clone inserts were sequenced, and 62,988 BAC-end sequence (BES) pairs were mapped onto the C57BL/6J genome, covering 89% of the total genome. Taking advantage of the BES map data, we established a computer-based clone screening system. Comparison of the MSM/Ms and C57BL/6J sequences revealed 489,200 candidate single nucleotide polymorphisms (SNPs). The overall nucleotide substitution rate was as high as 0.0096. The distribution of SNPs along the C57BL/6J genome was not uniform : The majority of the genome showed a high SNP rate, and only 5.2% of the genome showed an extremely low SNP rate; these sequences are likely derived from the molossinus genome.
It is believed that subspecies molossinus has contributed substantially to the genome constitution of common laboratory strains of mice, although the majority of their genome is derived from the west European M. m. domesticus. Information on the molossinus genome is thus essential not only for genetic studies involving molossinus but also for characterization of common laboratory strains.
We also used these BAC clones for making transgenic animals. We could detect expression of transgenes contained in the BAC clone taking advantage of SNPs frequently found between MSM/Ms and laboratory strain used for transgenesis. We could successfully rescue embryonic lethal phenotype of t^<w5> mutation mapped on mouse chromosome 17, and proved utility of MSM BAC transgenesis in functional genomic analyses in mice.
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