Functional alterations in gap junction channels formed by mutant forms of connexin 32 evidence for loss of function as a pathogenic mechanism in the X linked form of Charcot Marie Tooth disease英文电子书.pdf

Brain Research 900 (2001) 9–25 /locate/bres Research report Functional alterations in gap junction channels formed by mutant forms of connexin 32: evidence for loss of function as a pathogenic mechanism in the X-linked form of Charcot-Marie-Tooth disease * Charles K. Abrams , Mona M. Freidin, Vytas K. Verselis, Michael V.L. Bennett, Thaddeus A. Bargiello Albert Einstein College of Medicine, 1300 Morris Park Avenue Bronx, NY 10463, USA Accepted 12 December 2000 Abstract CMTX, the X-linked form of Charcot-Marie-Tooth disease, is an inherited peripheral neuropathy arising in patients with mutations in the gene encoding the gap junction protein connexin 32 (Cx32). In this communication, we describe the expression levels and biophysical parameters of seven mutant forms of Cx32 associated with CMTX, when expressed in paired Xenopus oocytes. Paired oocytes expressing the R15Q and H94Q mutants show junctional conductances not statistically different from that determined for Cx32WT, though both show a trend toward reduced levels. The S85C and G12S mutants induce reduced levels of junctional conductance. Three other mutants (R15W, H94Y and V139M) induce no conductance above baseline when expressed in paired oocytes. Analysis of the conductance voltage relations for these mutants shows that the reduced levels of conductance are entirely (H94Y and V139M) or partly (S85C and R15W) explicable by a reduced open probab