Gene expression in the presence or absence of myelin assembly

Regulation of myelin protein gene expression in the presence and absence of myelin assembly can be assessed using crushed or permanently transected adult sciatic nerves of rats. The P0 glycoprotein and the myelin basic protein (MBP) are the major myelin-specific proteins of the peripheral nervous system. The steady-state level of P0 and MBP messenger RNA was determined by dot-blot analysis of poly(A)+ RNA from crushed and transected nerves of rats at 35 days post operation. The rat P0-specific cDNA clone, pSN63c, and mouse MBP-specific cDNA clone, pHF43, were used as probes. The level and quality of the poly(A)+ RNA was assessed by in vitro translation and immunoprecipitation of the translation products with anti-chick P0 antibody. Comparison of the steady-state level of P0 and MBP transcripts and the level of anti-P0 immunoprecipitated translation products from RNA extracts of permanently transected, crushed, adult control and 21-day-old control rat nerves indicated that the level of P0 and MBP messages was significantly reduced in the permanently transected model, whereas it was restored to normal in the crushed sciatic nerve 35 days post injury. These results suggest that regulation of P0 and MBP gene expression most likely occurs at the transcriptional or post-transcriptional level in the two models of peripheral neuropathies. Northern blot analysis indicated the absence of differential splicing of the message in crushed or transected nerves. The experiments also indicate that these two important gene products required for myelin synthesis and assembly seem to be co-regulated. However, the data do not rule out the possibility that regulation of gene expression may also occur at the level of translation or post-translational processing.