A Single Nucleotide Difference in the Gene for Myelin Proteolipid Protein Defines the Jimpy Mutation in Mouse |
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Authors: | †Klaus-Armin Nave Floyd E Bloom Robert J Milner |
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Institution: | Division of Preclinical Neuroscience and Endocrinology, Research Institute of Scripps Clinic, La Jolla, CA 92037. |
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Abstract: | 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. |
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Keywords: | Jimpy mouse Proteolipid protein DM-20 Mutation RNA splicing Myelin |
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