On the occurrence of hypomyelination in a transgenic mouse model: A consequence of the myelin basic protein promoter?

Stefanie Gaupp, Joseph Arezzo, Dipankar J. Dutta, Gareth R. John, Cedric S. Raine

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Central nervous system hypomyelination is a feature common to anumber of transgenic (Tg) mouse lines that express a variety of unrelated exogenous (i.e. non-central nervous system) transgenes. Inthis report, we document hypomyelination structurally by immunocytochemistry and functionally in the Tg line MBP-JE, which overexpresses the chemokine CCL2 (MCP-1) within oligodendrocytestargeted by a myelin basic protein (MBP) promoter. Analysis ofhypomyelinated optic nerves of Tg mice revealed progressive decrease in oligodendrocyte numbers with age (p < 0.01). Although molecular mechanisms underlying hypomyelination in this and other Tg models remain largely unknown, we present preliminary findings on oligodendrocyte progenitor cell (OPC) cultures in which, although OPC expressed CCR2, the receptor for CCL2, treatment with CCL2 had no significant effect on OPC proliferation, differentiation, or apoptosis. We suggest that hypomyelination in the MBP-JE model might not be due to CCL2 expression but rather the result of transcriptional dysfunction related to random insertion of the MBP promoter that disrupts myelinogenesis and leads to oligodendrocyte demise. Because an MBP promoter is a common denominator in most Tg lines displaying hypomyelination, we hypothesize that use of myelin gene sequences in the regulator region of Tg constructs might underlie thisperturbation of myelination in such models.

Original languageEnglish (US)
Pages (from-to)1138-1150
Number of pages13
JournalJournal of Neuropathology and Experimental Neurology
Volume70
Issue number12
DOIs
StatePublished - Dec 1 2011

Keywords

  • Apoptosis
  • Autoimmune demyelination
  • Chemokine
  • Multiple sclerosis
  • Myelination
  • Oligodendrocyte
  • Progenitor cells
  • Transcription
  • Transgenic mice

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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