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Papers In Press, published online ahead of print June 26, 2001
Pathology, Washington University School of Medicine, Saint Louis, MO 63110
Corresponding Author: jeff{at}pathbox.wustl.edu
Peripheral nerve injury results in axonal degeneration and in phenotypic changes of the surrounding Schwann cells, whose presence is critical for nerve regeneration. To identify genes induced after nerve injury in Schwann cells, we developed a strategy that included differential screening of a subtractive library enriched for cDNAs expressed in injured nerve, sequence analysis, and expression profiling. By using real-time quantitative RT-PCR, we found that injury-induced genes could be categorized into four temporal expression patterns. The majority of these injury-induced genes were expressed at high levels in early postnatal nerve, but their expression decreased as myelination ensued. Among the clones we identified were a number that were homologous only to ESTs in the database. These were stratified based on their expression profile, presence of identifiable sequence motifs, homologies to other proteins, and evolutionary conservation. We chose one representative gene, nin283, to analyze in detail. The nin283 gene encodes a 227-residue protein containing both a zinc finger and a RING finger motif. Expression analysis in rat revealed that nin283 is highly expressed in the CNS, particularly in the developing cortical plate in embryos. It is also expressed in peripheral ganglia and is induced by NGF in PC12 cells. Subcellular localization analysis demonstrated that nin283 is located in the endosome/lysosome compartment, suggesting that it may participate in ubiquitin-mediated protein modification. Through this stratification strategy, we have identified a number of novel nerve injury-induced genes that may provide new insight into the role of Schwann cells in nerve regeneration and development.
J. Biol. Chem, 10.1074/jbc.M104271200
Submitted on May 10, 2001
Revised on June 22, 2001
Accepted on June 26, 2001
Identification of genes induced in peripheral nerve after injury: Expression profiling and novel gene discovery
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