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Functional abnormalities in P 0 ‐deficient mice resemble human hereditary neuropathies linked to P 0 gene mutations
Author(s) -
Zielasek Jürgen,
Martini Rudolf,
Toyka Klaus V.
Publication year - 1996
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/(sici)1097-4598(199608)19:8<946::aid-mus2>3.0.co;2-8
Subject(s) - sciatic nerve , nerve conduction velocity , schwann cell , myelin , medicine , facial nerve , pathology , anatomy , biology , central nervous system
Mutations in the gene encoding the transmembranous cell adhesion molecule, myelin protein zero (P 0 ), have been reported in patients with Charcot‐Marie‐Tooth disease types 1B and 3 (Déjérine‐Sottas disease). We have previously shown that the targeted deletion of the P 0 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 P 0 (P 0 −/− mice). As compared to control mice (P 0 +/+ ), 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 P 0 (P 0 +/− ) 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, P 0 −/− mice resemble severe human inherited neuropathies like Charcot‐Marie‐Tooth disease type 3 (Déjérine‐Sottas disease) with onset early in life, whereas the P 0 +/− mice may resemble the milder form, CMT1B. © 1996 John Wiley & Sons, Inc.