The present work focuses on the study of genes associated with neuronal injury and nerve regeneration. We studied the regulation of SR13, a novel protein cloned from a sciatic nerve library. Our primary findings were as follows: (a) SR13 mRNA was localized to Schwann cells using in situ hybridization histochemistry, where it's expression was repressed after sciatic nerve transection; (b) SR 13-like immunoreactivity was found in neurons in the spinal cord and in fibers in both the dorsal root ganglia (DRG) and the spinal cord; (c) RNA blot analysis showed that SR13 message was induced in a Pheochromocytoma cell line (PC12) after nerve growth factor (NGF) treatment, suggesting that SR13 expression may be regulated by NGF. The significance of this project has recently become evident due to recent reports showing that the SR13 gene is mutated in trembler mice (a model for peripheral neuropathy). SR13 was found to be duplicated in patients with Charcot-marie-tooth disease (CMT), a common inherited neuropathy in humans that involves both motor and sensory nerves and has a prevalence rate of 1 in 2500. We continued the characterization of two cDNAs named DI12 and DA11. DI12 is similar to the human FK506BP and may play an important role in T cell activation. DA11 is a novel cDNA that is induced in the DRG after sciatic nerve cut. Its function is still unclear. Finally, we also examined the pattern of expression of the transcription factors jun-D, jun B, c-fos and c-jun in the DRG after nerve transection. We found that only the mRNA of c-jun was upregulated ipsilateral to the nerve transection. These data suggest that c-jun may play an important role in neuronal injury and nerve regeneration.
