Accelerated axonal loss following acute CNS demyelination in mice lacking protein tyrosine phosphatase receptor type Z

Am J Pathol. 2012 Nov;181(5):1518-23. doi: 10.1016/j.ajpath.2012.07.011. Epub 2012 Aug 31.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Axons / enzymology*
  • Axons / pathology*
  • Axons / ultrastructure
  • Cell Differentiation
  • Central Nervous System / enzymology*
  • Central Nervous System / pathology*
  • Central Nervous System / ultrastructure
  • Demyelinating Diseases / enzymology*
  • Demyelinating Diseases / pathology*
  • Mice
  • Oligodendroglia / enzymology
  • Oligodendroglia / pathology
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5 / deficiency
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5 / metabolism
  • Spinal Cord / enzymology
  • Spinal Cord / pathology
  • Spinal Cord / ultrastructure
  • Stem Cells / enzymology
  • Stem Cells / pathology


  • Ptprz1 protein, mouse
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5