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Organization and expression of the human myelin basic protein gene
J Kamholz1, J Toffenetti, R A Lazzarini
1Laboratory of Molecular Genetics, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, Maryland 20892.
Journal of Neuroscience Research
|September 1, 1988
Summary
Researchers characterized the human myelin basic protein (MBP) gene, revealing alternative splicing regulates the four MBP isoforms crucial for brain development. This complex process involves temporal and regional control during myelination.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- The human brain expresses four isoforms of myelin basic protein (MBP).
- Previous identification of these isoforms was achieved through cDNA cloning.
Purpose of the Study:
- To isolate and characterize genomic clones encoding the human MBP gene.
- To elucidate the mechanisms regulating the four human MBP isoforms and their role in myelination.
Main Methods:
- Isolation and characterization of genomic clones for the human MBP gene.
- Determination of intron-exon boundaries and splice sequences.
- Analysis of MBP gene transcription initiation and promoter region.
- RNase protection assays to quantify MBP mRNA levels in neonatal and adult brain RNA.
Main Results:
- The human MBP gene spans 45 kb and comprises seven exons.
- Alternative splicing of the primary MBP transcript accounts for all four human MBP isoforms.
- MBP transcription initiates from a single site within the promoter, which contains a unique 12-bp sequence.
- MBP transcription exhibits a caudal-to-rostral gradient in the developing brain, correlating with myelination patterns.
- Neonatal brain shows higher levels of 21.5-kD and 20.5-kD MBP mRNAs compared to adult frontal cortex, indicating temporal regulation of alternative splicing.
Conclusions:
- Myelination regulation is complex, involving cellular interactions, transcriptional control, and alternative splicing modulation.
- Alternative splicing plays a significant role in myelin biogenesis, as suggested by comparative human and mouse data.