Expression of the exon 1A-containing PMP22 transcript is altered in the trembler mouse

The trembler mouse suffers from a dominantly inherited mutation of the peripheral myelin protein 22 (PMP22) gene which results in an abnormal myelination of its peripheral nervous system. The recent identification of two different PMP22 mRNA differing in their 5' non-translated region led us to monitor their respective levels of expression in the trembler peripheral nervous system (PNS) during the myelination period. We showed that the steady-state levels of the exon 1A-containing transcript, which is thought to be involved in the myelination process, were greatly reduced in heterozygous and homozygous trembler mice when compared to the normal animals. Such a difference was not observed for the exon 1B-containing transcript. Therefore, our results support the idea that the two alternatively used promoters of the PMP22 gene are under different regulation control, and that the up-regulation of the exon 1A-transcript is necessary for the normal myelination of the mouse PNS.