title: Null mutations of connexin32 in patients with X-linked Charcot-Marie-Tooth disease.
abstract: The X-linked form of Charcot-Marie-Tooth disease (CMTX) is associated with mutations in the gene encoding connexin32, a member of the family of proteins forming intercellular channels. We have compared the functional properties of three mutant connexin32 genes with those of the wild-type gene by testing their ability to form intercellular channels in the paired oocyte expression system. Whereas wild-type connexin32 induced the development of large junctional conductance between paired oocytes, no functional channels were detected between pairs expressing CMTX mutants. Furthermore, CMTX mutants selectively acted as dominant inhibitors of intercellular communication by interfering with the channel-forming ability of connexin26 but not with that of connexin40. These results demonstrate a functional loss in the product of a candidate gene for a demyelinating form of CMT.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: R
authors.initials: R
authors.lastname: Bruzzone
authors.forename: T W
authors.initials: TW
authors.lastname: White
authors.forename: S S
authors.initials: SS
authors.lastname: Scherer
authors.forename: K H
authors.initials: KH
authors.lastname: Fischbeck
authors.forename: D L
authors.initials: DL
authors.lastname: Paul
mesh_terms: D000818:Animals; D001483:Base Sequence; D002450:Cell Communication; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D017630:Connexins / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D017629:Gap Junctions / Q000502:physiology*; D005799:Genes, Dominant; D008969:Molecular Sequence Data; D009865:Oocytes; D014960:X Chromosome; D014982:Xenopus laevis; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D017931:DNA Primers; D000097002:Gap Junction beta-1 Protein