CD44 overexpression by oligodendrocytes

A novel mouse model of inflammation-independent demyelination and dysmyelination

Therese M F Tuohy, Nicholas Wallingford, Ying Liu, Frank H. Chan, Tilat Rizvi, Rubing Xing, Bruce Bebo, Mahendra S. Rao, Lawrence (Larry) Sherman

    Research output: Contribution to journalArticle

    30 Citations (Scopus)

    Abstract

    The CD44 transmembrane glycoprotein family has been implicated in cell-cell adhesion and cell signaling in response to components of the extracellular matrix but its role in the nervous system is not understood. CD44 proteins are elevated in Schwann cells and oligodendrocytes following nervous system insults, in inflammatory demyelinating lesions, and in tumors. Here, we tested the hypothesis that elevated CD44 expression influences Schwann cell and oligodendrocyte functions by generating transgenic mice that express CD44 under the control of the 2′,3′-cyclic nucleotide-3′- phosphodiesterase (CNPase) promoter. These mice failed to develop peripheral nerve or CNS tumors. However, they did develop severe tremors that were associated with CNS dysmyelination and progressive demyelination. Loss of CNS myelin was not due to alterations in early oligodendrocyte precursor differentiation, proliferation, or survival. Myelination in the PNS appeared normal. In no instance was there any evidence of an inflammatory response that could account for the loss of CNS myelin. These findings suggest that CNPase-CD44 mice are a novel model for noninflammatory progressive demyelinating disease and support a potential role for CD44 proteins expressed by glial cells in promoting demyelination.

    Original languageEnglish (US)
    Pages (from-to)335-345
    Number of pages11
    JournalGLIA
    Volume47
    Issue number4
    DOIs
    StatePublished - Sep 2004

    Fingerprint

    Oligodendroglia
    Demyelinating Diseases
    Cyclic Nucleotides
    Schwann Cells
    Phosphoric Diester Hydrolases
    Myelin Sheath
    Inflammation
    Nervous System
    Tremor
    Peripheral Nerves
    Cell Adhesion
    Neuroglia
    Transgenic Mice
    Extracellular Matrix
    Neoplasms
    Glycoproteins
    Proteins

    Keywords

    • CD44
    • Demyelination
    • Dysmyelination
    • Oligodendrocyte
    • Schwann cell

    ASJC Scopus subject areas

    • Immunology

    Cite this

    CD44 overexpression by oligodendrocytes : A novel mouse model of inflammation-independent demyelination and dysmyelination. / Tuohy, Therese M F; Wallingford, Nicholas; Liu, Ying; Chan, Frank H.; Rizvi, Tilat; Xing, Rubing; Bebo, Bruce; Rao, Mahendra S.; Sherman, Lawrence (Larry).

    In: GLIA, Vol. 47, No. 4, 09.2004, p. 335-345.

    Research output: Contribution to journalArticle

    Tuohy, TMF, Wallingford, N, Liu, Y, Chan, FH, Rizvi, T, Xing, R, Bebo, B, Rao, MS & Sherman, LL 2004, 'CD44 overexpression by oligodendrocytes: A novel mouse model of inflammation-independent demyelination and dysmyelination', GLIA, vol. 47, no. 4, pp. 335-345. https://doi.org/10.1002/glia.20042
    Tuohy, Therese M F ; Wallingford, Nicholas ; Liu, Ying ; Chan, Frank H. ; Rizvi, Tilat ; Xing, Rubing ; Bebo, Bruce ; Rao, Mahendra S. ; Sherman, Lawrence (Larry). / CD44 overexpression by oligodendrocytes : A novel mouse model of inflammation-independent demyelination and dysmyelination. In: GLIA. 2004 ; Vol. 47, No. 4. pp. 335-345.
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