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

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