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The Journal of Neuroscience, July 1, 2002, 22(13):5481-5491

Enhanced Rate of Nerve Regeneration and Directional Errors After Sciatic Nerve Injury in Receptor Protein Tyrosine Phosphatase  Knock-Out Mice

Joanna McLean^{1, *}, Jane Batt^{2, *}, Laurie C. Doering⁴, Daniela Rotin², and James R. Bain³

¹ Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada, M5G 1X8, ² Program in Cell Biology, Hospital for Sick Children, and Department of Biochemistry and Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada, M5G 1X8, and Departments of ³ Surgery and ⁴ Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada, L8N 3Z5

The receptor protein tyrosine phosphatase  (PTP) is a member of the mammalian leukocyte common antigen-related (LAR) family. Its expression is developmentally regulated in neuronal tissues. The Drosophila homolog of the mammalian LAR family of phosphatases (DLAR) controls axon guidance during Drosophila embryogenesis. We have demonstrated previously that mice deficient in PTP have CNS and peripheral nervous system abnormalities. The sciatic nerve in the PTP(/) mice demonstrates an increased number of small diameter fibers and slower nerve conduction velocities compared with PTP(+/+) or PTP(+/) controls. To study whether peripheral nerve regeneration is affected by PTP activity, we assessed nerve regeneration in the PTP(/) mouse after three standard models of sciatic nerve injury. We report that after sciatic nerve crush injury, nerve regeneration was significantly faster in the PTP(/) animals, as determined by histologic, electrophysiologic, and neuromuscular testing. After sciatic nerve transection with immediate microsurgical repair or allografting, PTP(/) nerve fibers demonstrated errors in directional growth compared with controls. We propose that PTP regulates the axonal regeneration rate and guidance of regenerating fibers.

Key words: protein tyrosine phosphatase ; axon guidance; nerve regeneration; sciatic nerve; knock-out mouse; walking track analysis

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^* J.M. and J.B. contributed equally to this manuscript.

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22135481-11$05.00/0

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