Type 1B research from May 2002/Japan

[Guest guest]

Amelia,

This article on 1B is the most current I could find - from May 2002. ~

Gretchen

1: Acta Neuropathol (Berl) 2002 May;103(5):501-8

Altered trafficking and adhesion function of MPZ mutations and

phenotypes of Charcot-Marie-Tooth disease 1B.

Matsuyama W, Nakagawa M, Takashima H, Osame M.

Third Department of Internal Medicine, Kagoshima University Faculty of

Medicine, Sakuragaoka 8-35-1, Kagoshima City 890-8520, Japan.

We previously reported familial cases characterized by

Charcot-Marie-Tooth disease (CMT) phenotype with abnormal myelin

foldings and MPZ Ile62Phe mutation. To further clarify the molecular

mechanisms in this family, we produced wild-type MPZ, Ile62Phe mutant

and other mutations in the neighboring regions producing thin myelin

sheaths (Ser63del, Ser63Cys and Ser63Phe) by site-specific mutagenesis

and transfected these into rat pheochromocytoma cells (PC12). We

investigated the expression and aggregation properties of the MPZ

protein through immunoblotting, immunohistochemical staining and

adhesion assay. MPZ protein with Ile62Phe mutation was

immunohistochemically

detectable mainly in the plasma membrane of the cells, and it induced a

cell aggregation behavior different from the other mutations or the

wild-type MPZ. These studies suggested that MPZ Ile62Phe mutation in

CMT1B with abnormal myelin folding induced dysregulation of adhesion

function of the MPZ protein in a manner unlike those seen in cells with

other mutations. The present study provides evidence that the site and

nature of amino acid substitutions in the MPZ protein are closely

related

to the abnormal myelination in CMT1B.