| Project/Area Number |
16310133
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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 |
基礎ゲノム科学
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| Research Institution | University of Toyama |
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Principal Investigator |
ISOBE Masaharu University of Toyama, Faculty of Science and Engineering Graduate School, Professor (70211050)
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| Co-Investigator(Kenkyū-buntansha) |
KUROSAWA Nobuyuki University of Toyama, Faculty of Science and Engineering, Graduate School, Associate Professor (50241253)
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| Project Period (FY) |
2004 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,520,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2007: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2006: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2005: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥4,500,000 (Direct Cost: ¥4,500,000)
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| Keywords | SAM P8 / JF1 / QTL analysis / Learning and Memory Dysfunction / Senescence |
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| Research Abstract |
1) We have obtained F2 mice by mating P8 strain of Senescence Accelerated Mouse (SAMP8) exhibiting age related learning and memory dysfunction with Japanese wild mouse derived JF1 strain showing normal phenotype. We have performed genome-wide QTL analysis on these F2 mice at the age of 5 month by Step Through experiment with more than 120 genetic markers, and found four significant QTL loci on chromosomes 1, 13 and 15. Interestingly, while the candidate loci on Chromosomes 1 and 13 were derived from SAMP8 background, two loci on chromosome 15 were found to be from JF1 background despite it was used as normal control.
2) Three speed-congenic strains carrying either SAMP8 derived chromosomes 1, 13, or 15 in JF1 background were established by backcrossing F1 strain with JF1 strain.
3) By exhaustive analysis of each candidate regions, we found 3 and 1 genes on chromosomes 1 and 13 carry polymorphisms whose amino acid replacements were specific to the SAM strain, respectively. In 2 loci on chromosome 15, we found 7 and 2 genes carrying polymorphisms associated with amino acid replacements in JF1 strain, respectively.
4) The SAM strain specific polymorphism on chromosome 13 was found in a gene coding for an ion channel. When this gene was expressed in cultured cells, we found difference in ion permeability compared with normal control by patch clump methods. This difference suggests the involvement of the ion channel in learning and memory dysfunction although further characterizations are needed.
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