| Project/Area Number |
13671113
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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 |
Kidney internal medicine
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| Research Institution | Tazuke Kofukai Medical Research Institute |
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Principal Investigator |
EN Muso Tazuke Kofukai Medical Research Institute First Division Chief Researcher, 医学研究所・第1研究部, 研究主幹 (10190852)
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| Co-Investigator(Kenkyū-buntansha) |
ONO Takahiko Kyoto University, Cardiovascular Medicine Assistant, 医学研究科, 助手 (60243028)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | IgA nephropathy / High serum IgA / Polymeric IgA / QTL analysis / HIGA mouse / IgA nephropathy model mouse / Analysis of pathogic gene / glomerular IgA / 純系モデルマウス / polymeic IgA / 量的形質遺伝子座(QTL)解析 / Microssatellite marker / LOD score |
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| Research Abstract |
1. Quantitative trait locus (QTL) analysis of high IgA phenotype
From 35 to 50% of patients with IgA nephropathy have elevated serum IgA levels. High incidence of hyperserum IgA in IgA nephropathy indicates that the background of this disease may be related to the genes responsible for the IgA production. To identify the genetic locus of hyperserum IgA, glomerular IgA deposition and obesity of HIGA mice, quantitative trait locus (QTL) analysis was carried out, using 244 F2 mice derived from a cross between HIGA and BALB/c mice Two significant QTLs of hyperserum IgA were identified on chromosome (Chr) 2 (LOD = 5.01) and Chr 4 (LOD = 4.45) and a significant QTL of glomerular IgA was identified on Chr 15(LOD = 4.40) Serum IgA levels was weakly correlated with the intensity of glomerular IgA,however QTLs of hyperserum IgA was not significantly associated with glomerular IgA. On Chr 2,there was also an obesity QTL (LOD = 846) which was above 11 cM away from the QTL of hyperserum IgA and no correlation was observed between serum IgA levels and body weights in F2 mice Present findings indicate that the gene which is most responsible for glomerular IgA deposition was not related to hyperserum IgA and moreover, obesity QTL Was not apparently associated with IgA abnormality in HIGA mice
2. QTL analysis of polymeric IgA
Significant linkage of polymeric IgA in sera was identified around D12Mit263 on chromosome 12 with a Lod score of 15.4 D12Mit263 has been demonstrated to closely linkage to the gene of immunoglobulin heavy chain.
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