| Project/Area Number |
18500331
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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 |
Laboratory animal science
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| Research Institution | Showa University |
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Principal Investigator |
MORITA Hiroyuki Showa University, Department of Medicine, Associate Professor (00311994)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,790,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | experimental nephritis / focal segmental glomerulosclerosis (FSGS) / nephritis / susceptibility gene / SNP / proteinuria / 疾患感受性遺伝子 / 細胞外基質タンパク / コンドロイチン硫酸 / プロテオグリカン / 巣状糸球体硬化症 / 遺伝子変異 / 疾患発症感受性遺伝子 / 細胞外基質 |
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| Research Abstract |
Focal and segmental glomerulosclerosis (FSGS) is a frequent finding in the progression of chronic renal failure. We identified a FSGS susceptibility gene in the BUF/Mna rat, which locate on rat chromosome 13. In the [(BUF/Mna x WKY/NCrj)F1 x BUF/Mna] backcross rats, we found that there was a modifier gene on rat chromosome 8 and 9. The purpose of the present study is to identify the gene on rat chromosome 8. In the F2 backcross cohort, urinary protein excretion increased in those individuals who showed BUF/Mna homozygousity for the D8Mit5 and ACPH markers. Using the NCBI data base UniSTS site, DNA markers were picked up. Some of them showed length polymorphism between BUF/Mna and WKY/NCrj strains and were used in typing. The results of the typing, together with gene information obtained from Ensemble data base, led us construct a physical map that indicated a candidate region on rat chromosome 8 (81.6-86.6 Mb). There were 30 genes in the region. PCR direct sequencing was performed, and then coding sequence of these genes were determined in the BUF/Mna and WKY/NCrj strains. A point mutation, which results in leucine-prolin substitution, was found in interphotoreceptor matrix proteoglycan 1 (Impg1) gene. Specific antibodies were produced by the use of DNA synthesis method. However, the antibodies were not capable of staining rat tissues and organs. (Lama1 is a modifier gene candidate on rat chromosome 9. Immunohistochemical analysis clearly showed that Lamal is expressed in tubular basement membranes of the kidney.)
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