A critical role for the protein tyrosine phosphatase receptor type Z in functional recovery from demyelinating lesions.
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 lesions. 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 generation, migration or maturation 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 Rptpbeta), which is expressed primarily in the nervous system but also in oligodendrocytes, astrocytes and neurons. 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.
D000818:Animals; D002455:Cell Division; D002469:Cell Separation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics; D005434:Flow Cytometry; D005838:Genotype; D006801:Humans; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism / Q000502:physiology*; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D013116:Spinal Cord / Q000473:pathology
D009419:Nerve Tissue Proteins; C516895:PTPRZ1 protein, human; D017027:Protein Tyrosine Phosphatases; C516896:Ptprz1 protein, mouse; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5