Functional abnormalities in P-0-deficient mice resemble human hereditary neuropathies linked to P-0 gene mutations
Functional abnormalities in P-0-deficient mice resemble human hereditary neuropathies linked to P-0 gene mutations
复制标题
DOI：
10.1002/(sici)1097-4598(199608)19:8
复制
发表时间：
1996-08-01
期刊：
影响因子：
3.4
通讯作者：
Toyka, KV
中科院分区：
文献类型：
--
作者：
Zielasek, J;Martini, R;Toyka, KV
据报道，1B 型和 3 型腓骨肌萎缩症（Dejerine-Sottas 病）患者中编码跨膜细胞粘附分子髓磷脂蛋白零 (P-0) 的基因发生突变。我们之前已经证明，小鼠 P-0 基因的靶向缺失会导致坐骨神经传导受损，现在我们将详细的电生理学研究扩展到面神经。组织学检查显示周围神经严重髓鞘形成不足，我们发现 P-0 表达纯合缺陷小鼠（P-0(-/-) 小鼠）的面神经和坐骨神经出现严重髓鞘形成障碍的典型电生理征象，与对照小鼠（P-0(+/+)）相比，神经传导速度降低至 10% 以下，复合肌肉动作电位 (CMAP) 振幅降低降至 25% 以下，而 CMAP 持续时间和兴奋阈值显着增加。令人惊讶的是，P-0 杂合性缺陷 (P-0(+/-)) 小鼠的神经传导变化非常轻微，仅在坐骨神经中检测到，并且不会在 5-7 个月龄之前发生。它们在 12-13 个月大时更为突出。因此，P-0(-/-) 小鼠类似于严重的人类遗传性神经病，如在生命早期发病的 3 型夏科-马里-图思病（Dejerine-Sottas 病），而 P-0(+/-) 小鼠可能类似于较温和的形式 CMT1B。 (C) 1996 约翰威利父子公司
Mutations in the gene encoding the transmembranous cell adhesion molecule, myelin protein zero (P-0), have been reported in patients with CharcotMarie-Tooth disease types 1B and 3 (Dejerine-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 (Dejerine-Sottas disease) with onset early in life, whereas the P-0(+/-) mice may resemble the milder form, CMT1B. (C) 1996 John Wiley & Sons, Inc.