Rumpshaker‐like proteolipid protein (PLP) ratio in a mouse model with unperturbed structural and functional integrity of the myelin sheath and axons in the central nervous system
Copyright policy )Rumpshaker‐like proteolipid protein (PLP) ratio in a mouse model with unperturbed structural and functional integrity of the myelin sheath and axons in the central nervous system
AbstractThe gene plp on the X chromosome encodes the isoforms proteolipid protein (PLP) and DM20, two dominant integral membrane proteins of central nervous system (CNS) myelin. DM20 results from the activation of the cryptic splice site in exon III of the PLP gene. We inserted a sense‐orientated loxP flanked neomycin‐gene into intron III of the plp sequence, using homologous recombination in embryonic stem cells and generated the homozygous neoS mouse line. Unlike the previously described complete PLP/DM20 ablation (plp−/−), which has been obtained by introducing a neo‐gene in antisense‐orientation in the same position of intron III, the plp expression surprisingly revealed reduced mRNA levels. The PLP isoform was reduced to 50%, but DM20 expression was unaffected. This protein pattern resembles the expression profile of the PLP isoforms in the natural occurring rumpshaker mutant. Electron microscopic examination revealed a normal compaction of CNS‐myelin and maintenance of axon integrity. PLP expression levels of the wt control were recovered by Cre excision of the neo‐selection gene after intercrossing neoS mice and oligodendrocyte‐specific Cre‐mice. These data strongly hint at different functions of intron III in PLP/DM20‐specific splicing and mRNA stability. Furthermore evidence is provided for functionally affected translation products of the PLP gene in the rumpshaker mutant, whereas no PLP‐isoform occur in plp−/− mice generated by introducing a selectable marker into intron III in antisense orientation. GLIA 35:63–71, 2001. © 2001 Wiley‐Liss, Inc.
- University of Cologne Germany
- Anatomische Anstalt Germany
- University of Bonn Germany
Central Nervous System, Mice, Knockout, Transcription, Genetic, Stem Cells, Gene Expression Regulation, Developmental, Neomycin, Nerve Tissue Proteins, Axons, Introns, Alternative Splicing, Disease Models, Animal, Mice, Mice, Neurologic Mutants, Phenotype, Gene Targeting, Animals, RNA, Messenger, Myelin Proteolipid Protein, Myelin Sheath
Central Nervous System, Mice, Knockout, Transcription, Genetic, Stem Cells, Gene Expression Regulation, Developmental, Neomycin, Nerve Tissue Proteins, Axons, Introns, Alternative Splicing, Disease Models, Animal, Mice, Mice, Neurologic Mutants, Phenotype, Gene Targeting, Animals, RNA, Messenger, Myelin Proteolipid Protein, Myelin Sheath
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).5 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Average influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Average
Citations provided by BIP!Popularity provided by BIP!