title: Accelerated axonal loss following acute CNS demyelination in mice lacking protein tyrosine phosphatase receptor type Z.
abstract: Protein tyrosine phosphatase receptor type Z (Ptprz) is widely expressed in the mammalian central nervous system and has been suggested to regulate oligodendrocyte survival and differentiation. We investigated the role of Ptprz in oligodendrocyte remyelination after acute, toxin-induced demyelination in Ptprz null mice. We found neither obvious impairment in the recruitment of oligodendrocyte precursor cells, astrocytes, or reactive microglia/macrophage to lesions nor a failure for oligodendrocyte precursor cells to differentiate and remyelinate axons at the lesions. However, we observed an unexpected increase in the number of dystrophic axons by 3 days after demyelination, followed by prominent Wallerian degeneration by 21 days in the Ptprz-deficient mice. Moreover, quantitative gait analysis revealed a deficit of locomotor behavior in the mutant mice, suggesting increased vulnerability to axonal injury. We propose that Ptprz is necessary to maintain central nervous system axonal integrity in a demyelinating environment and may be an important target of axonal protection in inflammatory demyelinating diseases, such as multiple sclerosis and periventricular leukomalacia.
authors.affiliation: Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, United Kingdom.
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Huang
authors.forename: Carina C
authors.initials: CC
authors.lastname: Ferrari
authors.forename: Glaucia
authors.initials: G
authors.lastname: Monteiro de Castro
authors.forename: David
authors.initials: D
authors.lastname: Lafont
authors.forename: Chao
authors.initials: C
authors.lastname: Zhao
authors.forename: Paola
authors.initials: P
authors.lastname: Zaratin
authors.forename: Sandrine
authors.initials: S
authors.lastname: Pouly
authors.forename: Beatrice
authors.initials: B
authors.lastname: Greco
authors.forename: Robin J M
authors.initials: RJ
authors.lastname: Franklin
mesh_terms: D000818:Animals; D017209:Apoptosis; D001369:Axons / Q000201:enzymology* / Q000473:pathology* / Q000648:ultrastructure; D002454:Cell Differentiation; D002490:Central Nervous System / Q000201:enzymology* / Q000473:pathology* / Q000648:ultrastructure; D003711:Demyelinating Diseases / Q000201:enzymology* / Q000473:pathology*; D051379:Mice; D009836:Oligodendroglia / Q000201:enzymology / Q000473:pathology; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000172:deficiency / Q000378:metabolism; D013116:Spinal Cord / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D013234:Stem Cells / Q000201:enzymology / Q000473:pathology
chemical_list: C516896:Ptprz1 protein, mouse; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5