A single nucleotide difference in the gene for myelin proteolipid protein defines the jimpy mutation in mouse.
We have previously shown that, in the myelin-deficient jimpy mutant mouse, 74 nucleotides are absent from the mRNA for proteolipid protein (PLP) as a result of aberrant RNA processing. To define the exact site of the jimpy mutation, we have analyzed the PLP gene obtained from a jimpy mouse genomic library. We find that the nucleotide sequence that is absent from jimpy PLP mRNA is fully preserved in the jimpy PLP gene. The missing segment corresponds to a separate exon, equivalent to exon 5 of the human PLP gene. The nucleotide sequence at the 3' end of intron 4 in the jimpy PLP gene contains a single point mutation. A base change A----G in the 3' acceptor splice site has altered a position that is 100% conserved in all published splice acceptor sequences. We conclude that the primary genetic defect of the jimpy mouse is a single base change in the PLP gene disabling an invariant recognition sequence of RNA splicing.
D000818:Animals; D010582:Bacteriophage lambda / Q000235:genetics; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004274:DNA, Recombinant; D005091:Exons; D005260:Female; D006801:Humans; D051379:Mice; D008816:Mice, Jimpy; D008969:Molecular Sequence Data; D009154:Mutation; D009185:Myelin Proteins / Q000235:genetics*; D018991:Myelin Proteolipid Protein; D010957:Plasmids; D012333:RNA, Messenger / Q000235:genetics
D004274:DNA, Recombinant; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D012333:RNA, Messenger; D004247:DNA