Aberrant splicing of the C4 gene trans cript of H-2^k mouse strains coused by the insertion of a retroposon, B2.

• Project/Area Number: 05454205
• Research Category: Grant-in-Aid for General Scientific Research (B)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: Kanazawa University
• Principal Investigator: TAKAHASHI Morinobu Kanazawa University Cancer Research Institute professor, がん研究所, 教授 (80019877)
• Project Period (FY): 1993 – 1994
• Project Status: Completed (Fiscal Year 1994)
• Budget Amount: ¥6,700,000 (Direct Cost: ¥6,700,000); Fiscal Year 1994: ¥2,700,000 (Direct Cost: ¥2,700,000); Fiscal Year 1993: ¥4,000,000 (Direct Cost: ¥4,000,000)
• Keywords: Complement C4 / H-2^k strains / B2 rapetitise sequence / RNA splicing / Gene transfection / Hepatic cell / Macrophage / 遺伝子導入 / レトロポゾン / マウス補体C4 / RNAスプライシング / マクロファージ

Research Abstract

A retroposon B2 sequence is inserted into the 13 intron of the complement C4 gene of H-2^k derivred C4 strains that are characterized by the low C4 production. Aberrantly processed C4 mRNA and decreased level of C4 mRNA are detected in these mouse strains. To test the possible causal relationship between the B2 insertion and low C4 production in H-2^k derived strains, we constructed recombinant C4 gene with or without the B2 sequence and transfected them into cultured hepatoma cells. The transfection of recombinant C4 gene without the B2 sequence always resulted in the production of only normal C4 mRNA at the normal level, while transfection of recombinant C4 gene with the B2 sequence resulted in the abnormal splicing of C4 gene transcript and devreased level of normal C4 mRNA.
Tissue-specific regulation of RNA processing for C4 gene transcript in H-2^k mouse strains are identified by analyzing the C4 mRNA from various tissues. In contrast to hepatic cells, peritoneal macrophages from H-2^k derived mouse strains, produced only normally processed C4 mRNA at the normal level.

Research Products

• [Publications] Nonaka et al.: "Molecular cloning of a lamprey homologue of the mammalian MHC class III gene,complement factor B." Journal of Immunology. 152. 2263-2269 (1994)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Zheng,J.-H.et al.: "Tissue-specific RNA processing for the complement C4 gene transcript in the H-2^k mouse strain" Immunogenetics. 37. 390-393 (1993)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Zheng,Z.-H,et al.: "Insertion of the B2 Sequenees into intron13 is the only defed of the H-2^k C4 gene that causes low C4 production." Nucleic Acids Research. 20. 4975-4979 (1993)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Takahashi M.et al.: "Evalution and genetic regulation of comlement C3 and C4 genes" Progress in Immunology. 8. 517-523 (1993)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 高橋守信: "生体防御機能の分子機構" 南江堂 尾上薫,森良一、植田浩司 編, 116 (1993)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nonaka, M.et al.: "Molecular cloning of a lamprey homologue of the mammalian MHC class III gene, complement factor B." Journal of Immunology. 152. 2263-2269 (1994)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Zheng, J.-H.et al.: "Tissue specific RNA processing for the complement C4 gene transcript in the H-2^k mouse strain." Immunogenetics. 37. 390-393 (1993)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Zheng.J.-H.: "Insertion of the B2 sequences into intron 13 is the only defect of the H-2^k C4 gene that causes low C4 production." Nucleic Acids Research. 20. 4975-4979 (1993)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Takahashi, M.et al.: "Evolution and genetic regulation of complement C3 and C4 genes." Progress in Immunology. 8. 517-523 (1993)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nonaka M.et al.: "Molecular cloning of a lamprey homologue of the mammalian MHC class III gene,compkment factor B" Journal of Immunelogy. 152. 2263-2269 (1994)
• [Publications] 高橋守信: "Tissue-specific RNA processing for complement C4 gene transcript in H-2^k mouse strains" Immunogenetics. 37. 390-393 (1993)
• [Publications] 高橋守信: "Molecular cloning of a lamprey homologue of the mommalian MHC class III gene complement factor B" Journal of Immunology. 152(in press). (1994)