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

在低产C4的H-2^k衍生C4菌株补体C4基因的第13内含子中插入一个逆转录子B2序列。在这些小鼠品系中检测到C4 mRNA的异常加工和C4 mRNA水平的降低。为了验证B2插入与H-2^k衍生菌株低C4产量之间可能的因果关系，我们构建了含有或不含B2序列的重组C4基因，并将其转染到培养的肝癌细胞中。转染不含B2序列的重组C4基因，只产生正常水平的正常C4 mRNA，而转染含B2序列的重组C4基因，导致C4基因转录物剪接异常，正常C4 mRNA水平下降。通过对不同组织C4 mRNA的分析，确定了H-2^k小鼠株C4基因转录物的组织特异性RNA加工调控。与肝细胞相比，来自H-2^k衍生小鼠品系的腹膜巨噬细胞仅产生正常水平的正常加工C4 mRNA。

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.