Abstract
Several lines of evidence suggest that tyrosine phosphorylation is a key element in myelin formation, differentiation of oligodendrocytes and Schwann cells, and recovery from demyelinating lesions1,2,3,4,5,6,7. Multiple sclerosis is a demyelinating disease of the human central nervous system, and studies of experimental demyelination indicate that remyelination in vivo requires the local generation8, migration or maturation9 of new oligodendrocytes, or some combination of these. Failure of remyelination in multiple sclerosis could result from the failure of any of these processes or from the death of oligodendrocytes. Ptprz encodes protein tyrosine phosphatase receptor type Z (Ptpz, also designated Rptpβ), which is expressed primarily in the nervous system but also in oligodendrocytes10,11, astrocytes and neurons12. Here we examine the susceptibility of mice deficient in Ptprz to experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. We observe that mice deficient in Ptprz show impaired recovery from EAE induced by myelin oligodendrocyte glycoprotein (MOG) peptide. This sustained paralysis is associated with increased apoptosis of mature oligodendrocytes in the spinal cords of mutant mice at the peak of inflammation. We further demonstrate that expression of PTPRZ1, the human homolog of Ptprz, is induced in multiple sclerosis lesions and that the gene is specifically expressed in remyelinating oligodendrocytes in these lesions. These results support a role for Ptprz in oligodendrocyte survival and in recovery from demyelinating disease.
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Acknowledgements
G.C.F. is currently supported by the US National Multiple Sclerosis Society, J.R. is supported by the US National Institute of Health and National Multiple Sclerosis Society and S.H. was supported in part by Fédération pour la Recherche Medicare et l'association Contre le Cancer.
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Harroch, S., Furtado, G., Brueck, W. et al. A critical role for the protein tyrosine phosphatase receptor type Z in functional recovery from demyelinating lesions. Nat Genet 32, 411–414 (2002). https://doi.org/10.1038/ng1004
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DOI: https://doi.org/10.1038/ng1004
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