Functional abnormalities in P0-deficient mice resemble human hereditary neuropathies linked to P0 gene mutations
✍ Scribed by Jürgen Zielasek; Rudolf Martini; Klaus V. Toyka
- Book ID
- 102653124
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 581 KB
- Volume
- 19
- Category
- Article
- ISSN
- 0148-639X
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✦ Synopsis
Mutations in the gene encoding the transmembranous cell adhesion molecule, myelin protein zero (Po), have been reported in patients with Charcot-Marie-Tooth disease types 1 B and 3 (Dejerine-Sottas disease). We have previously shown that the targeted deletion of the Po gene in mice results in impairment of sciatic nerve conduction, and we now extend our detailed electrophysiologic investigation to the facial nerve. In concordance with histologic investigations which revealed severe hypomyelination in peripheral nerves we found the typical electrophysiologic signs of severe dysmyelination in both the facial and sciatic nerves in mice homozygously deficient for the expression of Po (Po/-mice). As compared to control mice (e"), nerve conduction velocities were reduced to below 10% and compound muscle action potential (CMAP) amplitudes to below 25%, while CMAP duration and excitation thresholds were markedly increased. Surprisingly, nerve conduction changes in mice heterozygously deficient for Po (6' ) were only mild, were detected only in the sciatic nerve, and occurred not before 5-7 months of age. They were more prominent at age 12-13 months. Thus, Kf mice resemble severe human inherited neuropathies like Charcot-Marie-Tooth disease type 3 (Dejerine-Sottas disease) with onset early in life, whereas the K' mice may resemble the milder form, CMTlB. 0 1996