Cellular localization of the disintegrin CRII-7/rMDC15 mRNA in rat PNS andCNS and regulated expression in postnatal development and after nerve injury

Disintegrins perform putative functions in cell adhesion, signaling and fus ion. We have isolated a 2815-bp rat cDNA (CRII-7) representing a transcript that is differentially expressed during sciatic nerve regeneration. Nucleo tide sequence comparison indicates that CRII-7 is the rat homologue to the recently cloned cDNAs MDC15 (ADAM 15) and metargidin (hMDC15) of mouse and human, respectively. The CRII-7 cDNA (rMDC15) encodes a membrane-anchored g lycoprotein of approximately 85 kDa containing a disintegrin and a metallop rotease domain. Cellular metalloprotease disintegrins are a family of prote ins (ADAMs or MDC proteins) with important roles, e.g., in cell-cell intera ctions during fertilization, muscle and nerve development, or tumor necrosi s factor-or (TNF-cw) cleavage. Northern blot analysis demonstrated a predom inant expression of CRII-7/rMDC15 in the nervous system (PNS and CNS) and l ung. Analysis of the CRII-7/rMDC15 transcript levels following peripheral n erve lesions demonstrated regulated mRNA expression during Wallerian degene ration and nerve regeneration. The steady-state levels of CRII-7/rMDC15 tra nscripts markedly increased within the first day after lesion and then stea dily decreased for at least 4 weeks. CRII-7/rMDC15 mRNA expression was furt her examined during postnatal development and maturation of rat sciatic ner ve and brain, as well as in cultured Schwann cells, meningeal fibroblasts, and astrocytes. In situ hybridization on paraffin sections showed the cellu lar localization of CRII-7/rMDC15 mRNA in Schwann cells and endothelial cel ls of peripheral nerve and in various neuronal populations in brain and spi nal cord. (C) 2000 Wiley-Liss, Inc.