| Abstract: |
The HLA-DR β protein, DR βIV, encoded by the DRB4 gene, is found on class II+ cells of all DR4, DR9, and most DR7 individuals. However, in some DR7 individuals (DR7, Dw11), the DR βIV protein cannot be detected. To investigate the molecular mechanism responsible for this defect in expression, two overlapping genomic clones encoding the defective DRB4 allele (DRB4-null) were isolated. Although restriction fragment length analysis demonstrated no obvious alterations in the DRB4-null gene, nucleotide sequence analysis revealed a single base substitution in the acceptor splice site at the 3′ end of the first intron, changing the normal AG dinucleotide to AA. The nucleotide sequences of all the exons and remaining splice junctions were identical to those of the normal DRB4 gene. The effect of the altered splice junction was evident from RNA blot analysis where inactivation of the normal splice site was found to result in a larger than normal DRB4 gene transcript. Thus, defective expression of the DRβIV protein results from incorrect processing of the mRNA from the DRB4-null allele. © 1989 Springer-Verlag. |
| Keywords: |
human cell; mutation; cell line; cloning, molecular; molecular sequence data; genetic engineering; cell culture; nucleotide sequence; hla dr antigen; hla-dr antigens; base sequence; genes, mhc class ii; rna splicing; normal human; restriction mapping; human; priority journal; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; hla-dr4 antigen
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