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

Abstract

Disintegrins perform putative functions in cell adhesion, signaling and fusion. We have isolated a 2815-bp rat cDNA (CRII-7) representing a transcript that is differentially expressed during sciatic nerve regeneration. Nucleotide 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 glycoprotein of approximately 85 kDa containing a disintegrin and a metalloprotease domain. Cellular metalloprotease disintegrins are a family of proteins (ADAMs or MDC proteins) with important roles, e.g., in cell-cell interactions during fertilization, muscle and nerve development, or tumor necrosis factor-alpha (TNF-alpha) cleavage. Northern blot analysis demonstrated a predominant expression of CRII-7/rMDC15 in the nervous system (PNS and CNS) and lung. Analysis of the CRII-7/rMDC15 transcript levels following peripheral nerve lesions demonstrated regulated mRNA expression during Wallerian degeneration and nerve regeneration. The steady-state levels of CRII-7/rMDC15 transcripts markedly increased within the first day after lesion and then steadily decreased for at least 4 weeks. CRII-7/rMDC15 mRNA expression was further examined during postnatal development and maturation of rat sciatic nerve and brain, as well as in cultured Schwann cells, meningeal fibroblasts, and astrocytes. In situ hybridization on paraffin sections showed the cellular localization of CRII-7/rMDC15 mRNA in Schwann cells and endothelial cells of peripheral nerve and in various neuronal populations in brain and spinal cord.