CD44 overexpression by oligodendrocytes: a novel mouse model of inflammation-independent demyelination and dysmyelination.
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.
Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton 97006, USA. ShermanL@ohsu.edu
Therese M F
TM
Tuohy
Nicholas
N
Wallingford
Ying
Y
Liu
Frank H
FH
Chan
Tilat
T
Rizvi
Rubing
R
Xing
Bruce
B
Bebo
Mahendra S
MS
Rao
Larry S
LS
Sherman
D000818:Animals; D001259:Ataxia / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D002455:Cell Division / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D003711:Demyelinating Diseases / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D015870:Gene Expression / Q000276:immunology; D005911:Gliosis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D018960:Hyaluronan Receptors / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009443:Neuritis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology*; D012583:Schwann Cells / Q000473:pathology / Q000502:physiology; D014202:Tremor / Q000276:immunology / Q000473:pathology / Q000503:physiopathology
D018960:Hyaluronan Receptors