Identification of genes induced in peripheral nerve after injury - Expression profiling and novel gene discovery

Peripheral nerve injury results in axonal degeneration and in phenotypic ch anges of the surrounding Schwann cells, whose presence is critical for nerv e regeneration. To identify genes induced after nerve injury in Schwann cel ls, we developed a strategy that included differential screening of a subtr active library enriched for cDNAs expressed in injured nerve, sequence anal ysis, and expression profiling. By using real time quantitative reverse tra nscriptase-polymerase chain reaction, we found that injury-induced genes co uld be categorized into four temporal expression patterns. Among the clones we identified were a number that were homologous only to expressed sequenc e tags in the data base. These were stratified based on their expression pr ofile, presence of identifiable sequence motifs, homologies to other protei ns, and evolutionary conservation. We chose one representative gene, nin283 , to analyze in detail. The nin283 gene encodes a 227-residue protein conta ining both a zinc finger and a RING finger motif. nin283 is highly expresse d in the central nervous system, particularly in the developing cortical pl ate in embryos. It is also expressed in peripheral ganglia and is induced b y nerve growth factor in PC12 cells. Subcellular localization analysis demo nstrated that Nin283 is located in the endosome/lysosome compartment, sugge sting that it may participate in ubiquitin-mediated protein modification.