STRUCTURAL ABNORMALITIES AND DEFICIENT MAINTENANCE OF PERIPHERAL-NERVE MYELIN IN MICE LACKING THE GAP JUNCTION PROTEIN CONNEXIN-32

Mutations affecting the connexin 32 (Cx32) gene are associated with th e X-linked form of the hereditary peripheral neuropathy Charcot-Marie- Tooth disease (CMTX). We show that Cx32-deficient mice develop a late- onset progressive peripheral neuropathy with abnormalities comparable to those associated with CMTX, thus providing proof of the critical ro le of Cx32 in the maintenance of peripheral nerve myelin and an animal model for CMTX. Frequently observed features include abnormally thin myelin sheaths, cellular onion bulb formation reflecting myelin degene ration-induced Schwann cell proliferation, and enlarged periaxonal col lars while nerve conductance properties are altered only slightly. The se observations are consistent with earlier hypotheses suggesting a fu nction of Cx32 as a channel-forming protein that facilitates the commu nication between the abaxonal and adaxonal aspects of Schwann cell cyt oplasm.