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Nucleic Acids Research, 1992, Vol. 20, No. 19 4975-4979
© 1992

MOLECULAR BIOLOGY

Insertion of the B2 sequence into intron 13 is the only defect of the H-2k C4 gene which causes low C4 production

Jia Hua Zheng, Shunnosuke Natsuume-Sakai, Morinobu Takahashi and Masaru Nonaka*

Department of Immunobiology, Cancer Research Institute, Kanazawa University 13-1 Takaramachi, Kanazawa 920, Japan

* To whom correspondence should be addressed

Received August 11, 1992. Revised September 8, 1992. Accepted September 8, 1992.

The serum level of the fourth component of complement (C4) in mice bearing H-2k haplotype is only 1/10 of that of non-H-2k mice. H-2k bearing mice, but not non-H-2k bearing mice, have an insertion of the B2 sequence into intron 13 of the C4 gene, and aberrant C4 mRNA in liver apparently generated by abnormal RNA splicing caused by the insertion of the B2 sequence. To test the possible causal relationship between the B2 insertion and low C4 production in H-2k mice directly, we constructed the H-2k C4 gene without the B2 insertion and the H-2w7 (non-H-2k) C4 gene with the B2 insertion by exchanging a part of intron 13 between these two genes. Transfedion of the intact H-2w7 C4 gene or the chlmeric H-2k gene without the B2 insertion into HepG2 cells resulted in the production of only normal C4 mRNA at the normal level. On the other hand, the Intact H-2k C4 gene or the chimeric H-2w7 C4 gene with the B2 Insertion directed production of both aberrant and a decreased amount of normal C4 mRNA. These results demonstrated that the insertion of B2 sequence into intron 13 of the C4 gene is the only determinant of low C4 production by H-2k mice through aberrant RNA processing.


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