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The duplicated myelin basic protein gene in mld mutant mice does not impair transcription
1Laboratoire de Neurochimie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Abstract:
Myelin basic protein (MBP) gene organization and expression were analyzed in wild type and myelin deficient (mld) mutant mice. Southern analysis demonstrated MBP gene duplication in mld mice. In addition, we present evidence that one MBP gene in mld mice is normal for at least 14 kilobases (kb) upstream from exon I, whereas the second gene is normal for at least 3.5 kb but not more than 7 kb upstream from exon I. Run-on experiments showed that the rate of MBP gene transcription in mld mice is similar to that seen in normal mice. Detailed analysis of the transcriptional activity of various regions of the gene led us to conclude that all portions of the MBP gene are transcribed in mld mice. Consequently, we propose that the low levels of MBP mRNA observed in these mice (2-5% of the wild-type level) are not due to deficient transcriptional activity.
Insights
Myelin basic protein (MBP) gene duplication occurs in myelin deficient (mld) mice. Despite normal transcription rates, mld mice exhibit low MBP mRNA levels, suggesting post-transcriptional regulation.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Myelin basic protein (MBP) is crucial for myelin sheath formation in the central nervous system.
- Myelin deficient (mld) mice exhibit neurological deficits due to impaired myelination.
Purpose of the Study:
- To investigate the genetic organization and expression of the MBP gene in mld mice.
- To determine the cause of low MBP mRNA levels in mld mice.
Main Methods:
- Southern blot analysis to assess MBP gene structure.
- Run-on transcription assays to measure MBP gene transcriptional activity.
- Analysis of transcriptional activity across different gene regions.
Main Results:
- MBP gene duplication was identified in mld mice.
- Transcriptional activity of the MBP gene in mld mice was comparable to wild-type mice.
- All portions of the MBP gene were found to be transcribed in mld mice.
Conclusions:
- The low levels of MBP mRNA in mld mice are not attributable to reduced transcriptional activity.
- These findings suggest that post-transcriptional mechanisms likely regulate MBP mRNA levels in mld mice.