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.Fil: Huang, Jeffrey K.. University of Cambridge; Estados UnidosFil: Ferrari, Carina Cintia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Cambridge; Estados UnidosFil: Monteiro De Castro, Glaucia. University of Cambridge; Estados Unidos. Universidade Federal de Sao Paulo; BrasilFil: Lafont, David. Merck Serono International; SuizaFil: Zhao, Chao. University of Cambridge; Estados UnidosFil: Zaratin, Paola. Merck Serono International; SuizaFil: Pouly, Sandrine. Merck Serono International; SuizaFil: Greco, Beatrice. Merck Serono International; SuizaFil: Franklin, Robin J.M.. University of Cambridge; Estados Unidos