CMT X: The effects of a dominant connexin32 mutant in myelinating Schwann cells

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Mol Cell Neurosci. 2006 Jun 19

The effects of a dominant connexin32 mutant in myelinating Schwann

cells.

Jeng LJ, Balice-Gordon RJ, Messing A, Fischbeck KH, Scherer SS.

Cell and Molecular Biology Graduate Group, The University of

Pennsylvania Medical Center, Philadelphia, PA 19104-6077, USA.

Mutations in GJB1, the gene encoding the gap junction protein

connexin32 (Cx32), cause X-linked Charcot-Marie-Tooth disease, an

inherited demyelinating peripheral neuropathy. We generated

transgenic mice that express the R142W mutation in myelinating

Schwann cells. The R142W mutant protein was aberrantly localized to

the Golgi, indicating that it does not traffic properly, but the

molecular organization of the myelin sheath, including the

localization of Cx29, another connexin expressed by myelinating

Schwann cells, was not disrupted. In a wild type background, this

mutation dramatically decreased the level of wild type mouse Cx32 in

immunoblots of sciatic nerve and caused demyelination. The expression

of wild type human Cx32 with the same transgenic construct had

different effects-increased amounts of Cx32, normal localization of

Cx32 at nodes and incisures, and split myelin sheaths. Thus, the

R142W mutant protein has dominant effects that are distinct from

overexpression.