2013 Fiscal Year Research-status Report
ICGN マウスを用いた慢性腎臓病に対する抵抗性/感受性遺伝子の同定
| Project/Area Number |
25430083
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Research Institution | Kitasato University |
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Principal Investigator |
佐々木 宣哉 北里大学, 獣医学部, 教授 (20302614)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | ICGN mouse / chronic kidney disease / glomerulosclerosis / anemia / proteinuria |
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| Research Abstract |
The ICR-derived glomerulonephritis (ICGN) mouse is a chronic kidney disease (CKD) model that is characterized histologically by glomerulosclerosis, vascular sclerosis and tubulointerstitial fibrosis, and clinically by proteinuria and anemia, which are common symptoms and pathological changes associated with a variety of kidney diseases. Previously, we performed a quantitative trait locus (QTL) analysis to identify the causative genes for proteinuria in ICGN mice, and found a deletion mutation of the tensin 2 gene. Interestingly, the congenic strain carrying the Tns2nph mutation on a C57BL/6J (B6) genetic background exhibited milder phenotypes than did ICGN mice, indicating the presence of several modifier genes controlling the disease phenotype. In this study, to identify the modifier/resistant loci for CKD progression in Tns2-deficient mice, we performed QTL analysis using backcross progenies from susceptible ICGN and resistant B6 mice. We identified a significant locus on chromosome (Chr) 2 (LOD = 5.36; 31 cM) and two suggestive loci on Chrs 10 (LOD = 2.27; 64 cM) and X (LOD = 2.65; 67 cM) with linkage to the severity of tubulointerstitial injury. One significant locus on Chr 13 (LOD = 3.49; approximately 14 cM) and one suggestive locus on Chr 2 (LOD = 2.41; 51 cM) were identified as QTLs for the severity of glomerulosclerosis. Suggestive locus in BUN was also detected in the same Chr 2 region (LOD = 2.34; 51 cM). A locus on Chr 2 (36 cM) was significantly linked with HGB (LOD = 4.47) and HCT (LOD = 3.58).
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Progressing rather smoothly.
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| Strategy for Future Research Activity |
To validate the phenotypic effects of these loci, and to narrow down the critical region of the QTLs, we will create congenic mouse lines carrying different segments of the QT region from B6 introgressed into the ICGN background. Further, we will find the presence of non-synonymous coding SNPs or deletion in QTL using Exome sequencing.
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| Expenditure Plans for the Next FY Research Funding |
北海道大学から北里大学に移ったことから、研究のスタートが遅れたため。
新しい研究室がおおむねセットアップできたため、研究の遅れを挽回できる体制が整った。
今後は当初の計画通り執行する予定である。
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