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Mutations in the Myelin Proteolipid Protein Gene Alter Oligodendrocyte Gene Expression in Jimpy and Jimpy msd Mice
Author(s) -
Macklin Wendy B.,
Gardinier Minnetta V.,
Obeso Zaida O.,
King Kit D.,
Wight Patricia A.
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb02576.x
Subject(s) - mutant , microbiology and biotechnology , gene , proteolipid protein 1 , biology , exon , transcription (linguistics) , gene expression , myelin proteolipid protein , point mutation , myelin , genetics , myelin basic protein , endocrinology , linguistics , philosophy , central nervous system
The mouse myelin proteolipid protein (PLP) gene has been studied in normal and jimpy msd mice. Potential upstream regulatory regions of the normal gene have been cloned and mapped, but when these regions were studied in jimpy msd mice by Southern blots, no alterations were observed, relative to the normal gene. To assess whether the low ratio of PLP to DM20 proteins in this mutant reflected an altered PLP/DM20 ratio mRNAs, S1 nuclease analyses were undertaken, which demonstrated that at all ages studied in both jimpy and jimpy msd mice, PLP mRNA was elevated above DM20 mRNA. When exon 3 (the site of the alternative splice signal for DM20 mRNA) of the jimpy msd PLP gene was sequenced, no mutation was identified. The transcription of the PLP gene in normal and mutant animals was studied. The transcription rate increases in normal animals with development, and in very young jimpy msd or jimpy mice, the transcription rate of the PLP gene was close to that of agematched normal animals. However, by 10 days of age, the transcription rate of this gene in both mutants was significantly below that of age‐matched controls. The transcription rate of the myelin basic protein (MBP) gene was also reduced, indicating that expression of both genes is affected by this mutation. In contrast, the transcription rate of the glycerol phosphate dehydrogenase (GPDH) gene, an early marker of oligodendrocytes, is equal to or greater than normal in both mutants. We have confirmed an earlier report of a point mutation in exon 6 of the jimpy msd PLP gene, which converts an alanine to a valine. This mutation apparently alters oligodendrocyte metabolism such that the cell can differentiate to express early oligodendrocyte genes such as GPDH, but it cannot differentiate to a stage where it expresses the PLP and MBP genes at normal high levels.