WIDESPREAD EXPRESSION OF THE PERIPHERAL MYELIN PROTEIN-22 GENE (PMP22) IN NEURAL AND NONNEURAL TISSUES DURING MURINE DEVELOPMENT

The gene encoding the peripheral myelin protein PMP22 is affected by v arious mutations in the hereditary peripheral neuropathies Charcot-Mar ie-Tooth disease type 1A (CMT1A), Dejerine-Sottas syndrome (DSS) and h ereditary neuropathy with liability to pressure palsies (HNPP). In con trast to the recent remarkable progress in the genetics of the PMP22 g ene, the biological function of PMP22 remains largely unknown. In this report, we have confirmed by using in situ hybridization techniques t hat high levels of PMP22 mRNA are present in maturing peripheral nerve s of the 2-week-old mouse, a finding consistent with the PNS-specific defect observed in hereditary peripheral neuropathies. However, high l evels of PMP22 transcripts were also found in the villi of the adult g ut, and PMP22 expression was detected in various non-neural tissues du ring embryonic mouse development. In early embryogenesis (9.5 days pos tconception, dpc), PMP22 RNA expression appears restricted to the epit helial ectodermal layer. During early organogenesis (11.5 dpc), partic ularly high levels of expression are present in the capsule surroundin g the liver and in the forming gut, while low levels of PMP22 mRNA can be found in precartilagous condensations forming the vertebrae and th e ventricular layer of the myelencephalon. During midgestation develop ment (14.5 dpc to 16.5 dpc), the number of PMP22-positive tissues incr eases, and high expression is detected in several mesoderm-derived tis sues, in particular connective tissues of the face region, bones inclu ding the vertebrae, the lung mesenchym, and in muscles. In addition, h igh expression is also found in ectoderm-derived tissues, especially t he epithelia of the lens and the skin. These findings strongly suggest that PMP22 serves not only a PNS-specific function but is also of bro ader biological significance in cell proliferation and/or differentiat ion. (C) 1995 Wiley-Liss, Inc.