Expression pattern of the peripheral myelin protein 22kDa (PMP22) in neural and non-neural tissue types of adult wildtype and Trembler mice--a comparative study.

The Trembler mouse was the first animal model for Charcot-Marie-Tooth disease type 1 (CMT1), one of the most frequent inherited peripheral neuropathies in man. In Trembler mouse a Gly150Asp amino acid exchange in the peripheral myelin protein 22kDa (PMP22) gene was identified as causative reason for this hypertrophic neuropathy. For most of the CMT patients suffering from the subtype 1A a duplication of the PMP22 gene is found (gene dosage effect); but several PMP22 point mutations, such as that determining the TremblerJ mouse, have also been described. Since PMP22 is expressed in neural, as well as in non-neural tissues, the expression pattern of PMP22 in different tissues seems to be of highest interest for a better understanding of the hypothesized dual function of this protein. We studied different wildtype (wt) and Trembler (Tr) mouse tissues for PMP22 expression by means of radioactive in situ hybridization (RISH) and immunohistochemistry. A PMP22 expression was found in some of the non-neural and in all neural tissue types studied. Our in situ study clearly demonstrated, that PMP22 mRNA expression in non-neural tissues is not due to peripheral innervation. In non-neural tissues no difference in the expression pattern or intensity between wt and Tr mice was detectable, whereas PMP22 expression in the peripheral nervous system (PNS) of the Tr mouse was extremely reduced. Immunohistochemical analysis of sciatic nerve sections revealed the same maldistribution of PMP22 in Tr mice as in sural nerve biopsies of CMT1 patients.