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

Abstract

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. The<i>Drosophila</i> homolog of the mammalian LAR family of phosphatases (DLAR) controls axon guidance during<i>Drosophila</i> 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.