DIFFERENTIAL EXPRESSION OF 2 MESSENGER-RNA SPECIES INDICATES A DUAL FUNCTION OF PERIPHERAL MYELIN PROTEIN PMP22 IN CELL-GROWTH AND MYELINATION

Two peripheral myelin protein PMP22 transcripts, CD25 and SR13, have b een identified by Northern blot and RNA-polymerase chain reaction (PCR ) methods in rat. The CD25 and SR13 mRNA species (each approximately 1 .8 kb in size) differ significantly in their 5'-untranslated region (5 '-UTR) sequences but encode the same protein. While CD25 mRNA is large ly confined to the peripheral nervous system, the SR13 transcript is m ore ubiquitously expressed in rat tissues. Both transcripts are differ entially expressed during postnatal sciatic nerve development. While C D25 expression steadily increases from low levels in neonates up to a maximum at postnatal day 14, SR13 mRNA levels are elevated at birth bu t decrease throughout adulthood. CD25 and SR13 transcripts are express ed at very low constant levels in developing and adult brain. In degen erating and regenerating segments of injured peripheral nerve changes in CD25 mRNA levels clearly resemble the expression pattern of other m yelin genes, whereas expression of SR13 is inversely correlated with t he time course of Schwann cell proliferation. In cultured rat meningea l fibroblasts SR13 mRNA expression is strictly growth arrest-specific and independent of forskolin. On the other hand, regulation of CD25 mR NA levels in these cells is more complex with respect to interfering e ffects of serum and forskolin. In cultured Schwann cells neither CD25 nor SR13 expression is growth arrest-specific. However, both transcrip t levels are consistently enhanced by forskolin under all conditions o f cell growth tested. Expression of CD25 (but not SR13) depends on hig h Schwann cell density. Our results substantiate the hypothesis that P MP22 serves two biological functions, one related to cell growth (SR13 ) and another to myelination (CD25). (C) 1994 Wiley-Liss, Inc.