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

H-2^k 小鼠品系的 C4 基因转录的异常剪接是由逆转录子 B2 的插入引起的。

• 批准号: 05454205
• 负责人: TAKAHASHI Morinobu
• 金额: $ 4.29万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454205/
• 关键词: 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

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.

将逆转录子B2序列插入H-2^k衍生的C4菌株的补体C4基因的第13内含子中，所述菌株的特征在于C4产量低。在这些小鼠品系中检测到异常加工的C4 mRNA和C4 mRNA水平降低。为了验证B2插入与H-2^k衍生株中C4产量低之间的可能因果关系，我们构建了含或不含B2序列的重组C4基因，并将其转染培养的肝癌细胞。不含B2序列的重组C4基因的转染总是导致仅产生正常水平的正常C4 mRNA，而转染B2序列的重组C4基因则导致C4基因转录本的异常剪接和正常C4 mRNA水平的降低。k小鼠品系通过分析来自各种组织的C4 mRNA来鉴定。与肝细胞相反，H-2^k衍生小鼠品系的腹腔巨噬细胞仅产生正常水平的正常加工的C4 mRNA。

项目成果

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)

Cheng,J.-H.等人：“H-2^k 小鼠品系中补体 C4 基因转录物的组织特异性 RNA 处理”免疫遗传学。

Takahashi, M.et al.: "Evolution and genetic regulation of complement C3 and C4 genes." Progress in Immunology. 8. 517-523 (1993)

Takahashi, M.et al.：“补体 C3 和 C4 基因的进化和遗传调控。”

Takahashi M.et al.: "Evalution and genetic regulation of comlement C3 and C4 genes" Progress in Immunology. 8. 517-523 (1993)

Takahashi M.et al.：“补体 C3 和 C4 基因的评估和遗传调控”免疫学进展。

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)

Cheng.J.-H.：“将 B2 序列插入内含子 13 是 H-2^k C4 基因导致 C4 产量低的唯一缺陷。”

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)

Nonaka 等人：“哺乳动物 MHC III 类基因、补体因子 B 七鳃鳗同源物的分子克隆。”