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2002 Fiscal Year Final Research Report Summary

Quantitative trait locus analysis of genes responsible for the progression of IgA nephropathy - Analysis ofHIGA mice -

Research Project

Project/Area Number 13671113
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionTazuke Kofukai Medical Research Institute

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)

Co-Investigator(Kenkyū-buntansha) ONO Takahiko  Kyoto University, Cardiovascular Medicine Assistant, 医学研究科, 助手 (60243028)
Project Period (FY) 2001 – 2002
KeywordsIgA nephropathy / High serum IgA / Polymeric IgA / QTL analysis / HIGA mouse / IgA nephropathy model mouse / Analysis of pathogic gene / glomerular IgA
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.

  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Oyama A, et al.: "Up-regulated TGF-b mRNA expression in splenic T cells of high IgA-prone (HIGA) mice, a murine model of IgA nephropathy with glomerulosclerosis"Nephron. 88(4). 368-375 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ono T, et al.: "Coagulation process proceeds on cultured human mesangial cells via expression of factor V"Kidney Int. 60(3). 1009-1017 (2001)

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      「研究成果報告書概要(和文)」より
  • [Publications] Katsuma S, et al.: "Genomic analysis of a mouse model of immunoglobulin A nephropathy reveals an enhanced PDGF-EDG5 cascade"The Pharmacogenetics Journal. 1. 211-217 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 武曾 惠理: "Hyper IgA腎症モデル"BIOClinica. 16(12). 1127-1132 (2001)

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      「研究成果報告書概要(和文)」より
  • [Publications] Shirakawa K, et al.: "Correlation between the severity of clinicopathological parameters and whole blood interferon alpha production acapacity in active phase IgA nephropathy patients"Nephron. 90(1). 24-30 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kusano H, et al.: "Heminephrectomy causes the progression of glomerulonsclerosis and apoptosis in highIgA strain ddY mice"Nephron. 92(2). 389-398 (2002)

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      「研究成果報告書概要(和文)」より
  • [Publications] Makino T, et al.: "Suppressive effects of Perilla frutescens on IgA nephropathy in HIGA mice"Nephrol Dial Transplant. 18(3). 484-490 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kobayashi I, et al.: "Interleukin-12 alters the physicochemical characteristics of serum and glomerular IgA and modifies glycosylation in a ddY mouse strain having high IgA levels"Nephrol Dial Transplant. 17(12). 2108-2117 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kusano H, et al.: "Heminephrectomy causes the progression of glomerulosclerosis and apoptosis in high IgA strain of ddY (HIGA) mice"Nephrology. 6A4(suppl). (2002)

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      「研究成果報告書概要(和文)」より
  • [Publications] 武曾 恵理: "IgA腎症の発症と進展への対策"Nephrology Frontier. 1(3). 67-74 (2002)

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      「研究成果報告書概要(和文)」より
  • [Publications] 武曾 惠理: "第5章 原発性腎炎・ネフローゼの診断と治療.2.巣状糸球体硬化症. プラクティカル内科シリーズ10.腎炎・ネフローゼ"南江堂. 230 (2000)

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      「研究成果報告書概要(和文)」より
  • [Publications] 武曾 恵理: "治療方針・治療法A.一次性糸球体疾患.2.巣状分節状糸球体硬化症腎症腎疾患最新の治療2002-2004"南光堂. 305 (2002)

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      「研究成果報告書概要(和文)」より
  • [Publications] Nogaki F, Oida E, Kamata T, Kobayashi I, Nomura K, Suyama K Ono T , Miyawaki S , Kitada K , Serikawa T , Yoshida H., Kita T., Muso E.: "QTL analysis in a murine model of IgA neuropathy, a high serum IgA ddY mice"(in submission).

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      「研究成果報告書概要(欧文)」より
  • [Publications] Makino T., Ono T., Matsuyama K., Nogaki F., Miyawaki S., Honda G., Muso E.: "Suppressive effects of Perilla frutescens on IgA nephoropathy in HIGA mice in HIGA mice"Nephrol Dial Transplant. 18(3). 484-490 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kobayashi I, Nogaki F., Kusano H., Ono T., Miyawaki S., Yoshida H., Muso E: "Interleukin-12 alters the physicochemical chractaistics of serum and glomerular IgA and modifies glycosylation in a ddY mouse strain having high IgA levels"Nephrol Dial Transplant. 17(12). 2108-2117 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kusano H,Miyawaki S,Yosbida H,Ono T,Muso, E. Sasayama S.: "Heminephrectomy causes the progression of glomerulosclerosis and apoptosis in high IgA strain of ddY (HIGA)mice"Nephron. 92(2). 389-398 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsushima H., Yoshida H, Machiguchi T., Muso E., Tamura T.,Sasayama S.: "Urinary ablbmin and TGF β1 levels as renal damage indices in atients with congestive heart failure."Clin. Erp. Nephrol. (in print).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shirakawa K, Muso. E., Nogaki F., Maeda M., Kawamura T., Ono T., Yoshimoto M., Uno K., Kishida T., Sasayam S: "Correlation between the severity of clinicopathological parameters and whole blood interfeion alpha production capacity in active phase IgA nephropathy"Nephron. 90(1). 24-30 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] E Oida, F Nogaki, I Ko ayashi, T Kamata, T Ono, T Honjo, S Miyawaki, H Yoshida and E. Mus: "Genetic analysis in a high IgA strain of ddY(HIGA)mice"Nephrology. 26. A97 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Makino T, Ito M, Kiuchiu F, Ono T, Muso E, Honda G.: "Inhibitory effect of decoction of Perilla frutescens on cultured murine mesangial cell proliferation and quantitative analysis of its active constituents"Nephron. 92(2). 389-398 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Katsuma S., Shiojima., Hirasawa A., Suzuki Y, Takagaki K, Murai M., Kaminishi Y., Hada Y., Kova M., Muso. E., Miyawaki S., Ohgi T., Yano J., and Tsujimoto G.: "Suppressive effects of Perilla frutescens on mesangioproliferative glomerelonephritis in rats"Planta Med. 67(1). 24-28 (2001)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Yashiro M., Muso, E., Kamata T., Oyama A., Sasayama S. Yoshida H: "Genomio analysis of a mous e model of immunogloblin A nephorophathy reveals an enhanced PDGF-EDG5 cascade"The Pharmacogenetics Journal. 1. 211-317 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yashiro M., Muso, E., Kamata T., Oyama A., Sasayama S. Yoshida H: "Altered cultured mesangial cell phenotypes from RF/J mice ; A spontaneous immune comples mediated glomerulonephritis with progressive glomerulolsclerpsos"S Experimental Nephrol.. 89(4). 408-415 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Oyama A., Miso E., Ono T., Matsushima H., Yasihro M., Suyama K., Kamata T., Nogaki F., Kobayashi L, Miyamaki S., Yoshida H., Sasayama S.: "Up-regulated TGF-b mRNA exp. In splenic T coils of high IgA=prone (HIGA) mice, a murine model of IgA nephoropathy with glomerulosclerpsi"Nephron. 88(4). 368-375 (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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