Molecular defects in the non-expressed H-2 E alpha genes of the f and q haplotypes.
The expression and sequences of the mouse MHC class II genes, E alpha f and E alpha q, have been studied to determine the molecular basis for their defective expression. Previous work in our laboratory showed that H-2f and H-2q mice produce no detectable E alpha protein. Northern blot analysis confirms previous results showing normal amounts of E alpha f message and a 100-fold reduction in E alpha q mRNA. Despite that observation, the rates of transcription of both defective E alpha genes, measured by nuclear run-on transcription assays, are comparable to that of the normally expressed E alpha k gene. The nucleotide sequences of the E alpha f and E alpha q genes reveal mutations generating premature translation stop codons in both genes. A single base substitution has created the stop codon TGA at amino acid -2 in the E alpha f leader sequence. A nucleotide insertion at codon 64 in the second exon of the E alpha q gene results in a frame shift and a premature stop codon at amino acid residue 69 of a mature E alpha protein. The low steady state level of E alpha q mRNA may be correlated with the unusual size distribution of the RNA, possibly due to altered RNA processing.
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Department of Biological Sciences, Stanford University, CA 94305-5020.
Begovich
A B
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Tacchini-Cottier
F M
FM
Jones
P P
PP
D000818:Animals; D001483:Base Sequence; D006183:H-2 Antigens / Q000235:genetics*; D006239:Haplotypes; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D012333:RNA, Messenger / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D014158:Transcription, Genetic
D006183:H-2 Antigens; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell