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  • Upregulation of large myelin protein zero leads to Charcot-Marie-Tooth disease-like neuropathy in mice.

Upregulation of large myelin protein zero leads to Charcot-Marie-Tooth disease-like neuropathy in mice.

Communications biology (2020-03-15)
Yoshinori Otani, Nobuhiko Ohno, Jingjing Cui, Yoshihide Yamaguchi, Hiroko Baba
ABSTRACT

Charcot-Marie-Tooth (CMT) disease is a hereditary neuropathy mainly caused by gene mutation of peripheral myelin proteins including myelin protein zero (P0, MPZ). Large myelin protein zero (L-MPZ) is an isoform of P0 that contains an extended polypeptide synthesized by translational readthrough at the C-terminus in tetrapods, including humans. The physiological role of L-MPZ and consequences of an altered L-MPZ/P0 ratio in peripheral myelin are not known. To clarify this, we used genome editing to generate a mouse line (L-MPZ mice) that produced L-MPZ instead of P0. Motor tests and electrophysiological, immunohistological, and electron microscopy analyses show that homozygous L-MPZ mice exhibit CMT-like phenotypes including thin and/or loose myelin, increased small-caliber axons, and disorganized axo-glial interactions. Heterozygous mice show a milder phenotype. These results highlight the importance of an appropriate L-MPZ/P0 ratio and show that aberrant readthrough of a myelin protein causes neuropathy.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Potassium Channel Kv1.2 Antibody, clone K14/16, clone K14/16, from mouse
Sigma-Aldrich
Monoclonal Anti-Sodium Channel, Pan antibody produced in mouse, ~1 mg/mL, clone K58/35, purified immunoglobulin