Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 33

Abstract

CMT1A is a hereditary demyelinating neuropathy due to increased genetic dosage of peripheral myelin protein 22 (PMP22). The functions of PMP22 as a structural protein of peripheral myelin and a regulator of the proliferation, differentiation, shaping and apoptosis of Schwann cells (SCs) are well known. However, the effects of its overexpression on the molecular phenotype of SCs are still unclear. In order to detect genes that are modulated by PMP22 overexpression, we performed a cDNA microarrays experiment on PMP22 overexpressing sciatic nerves from a transgenic model of CMT1A. Differential expression of 117 known genes that are sensitive to PMP22 dosage was observed. The number of up‐ and down‐regulated genes in the transgenic nerves was 99 and 144 respectively, of 22.000 spotted genes. In the up‐regulated group, the number of known genes was 30 and the number of EST was 69. In the down‐regulated group, the number of known genes was 87 and that of EST 57. We classified the differentially expressed genes into functional categories. Among these, we focused our attention on groups of down‐regulated genes coding for cytoskeletal and transmembrane proteins and for extracellular matrix components, like collagens. Moreover we identified a group of genes with chromosomal localization in candidate regions for demyelinating neuropathies. The differential expression of several sequences was confirmed by RT‐PCR, performed both on normal and transgenic rat sciatic nerves, and on primary SCs cultures obtained from normal and CMT1A rats. Therefore, we point out the importance of the interaction between SCs and extracellular matrix and the involvement of SCs cytoskeletal organization in the pathogenesis of CMT1A. Moreover, this study suggests us new candidate genes that could be submitted to sequence analysis in demyelinating CMT.