Cifuentes-Diaz C, Velasco E, Meunier F A, Goudou D, Belkadi L, Faille L, Murawsky M, Angaut-Petit D, Molgó J, Schachner M, Saga Y, Aizawa S, Rieger F
Laboratoire Neuromodulations Interactives et Neuropathologies, INSERM, Paris, France.
Cell Mol Biol (Noisy-le-grand). 1998 Mar;44(2):357-79.
A thorough examination of the structure and plasticity of the neuromuscular system was performed in tenascin-C mutant mice deficient in tenascin-C. The study of the peripheral nerve revealed a number of abnormal features. In the motor nerve, numerous unmyelinated and myelinated fibers with degraded myelin were present. Schwann cell processes often enclosed degenerative terminals. Transgene (beta-galactosidase) expression analyzed at the ultrastructural level was found to be unequally distributed in the mutant's neuromuscular tissues. At the NMJ, preterminal disorganization was prevalent. Some axon terminals exhibited abnormal overgrowth. A surprising lack of beta-galactosidase expression at some cellular sites known to possess tenascin-C in wild type mice correlated best with marked changes in the cytoarchitecture of the peripheral nerve and NMJ. In some other -but not all- cellular sites which normally express the molecule, immunofluorescence analysis suggested the presence of significant but low levels of tenascin-C-like immunoreactivity together with beta-galactosidase expression. Messenger RNA detection by RT-PCR confirmed the presence of low amounts of tenascin-C mRNA in skeletal muscle suggesting that the mice deficient in tenascin-C are not complete knock-outs of this gene, but low-expression mutants. Following in vivo injections of botulinum type-A toxin, we observed a greatly reduced sprouting response of the motor nerves in tenascin-C mutant mice. We also observed that N-CAM and beta-catenin were overexpressed in the mutant. Our results suggest that tenascin-C is involved both in stabilization and in plasticity of the NMJ.
在缺乏腱生蛋白-C的腱生蛋白-C突变小鼠中，对神经肌肉系统的结构和可塑性进行了全面检查。对周围神经的研究发现了许多异常特征。在运动神经中，存在大量无髓鞘和髓鞘退化的有髓纤维。雪旺细胞突起常常包裹着退化的终末。在超微结构水平分析的转基因（β-半乳糖苷酶）表达在突变体的神经肌肉组织中分布不均。在神经肌肉接头处，终末前的紊乱很普遍。一些轴突终末表现出异常的过度生长。在野生型小鼠中已知含有腱生蛋白-C的一些细胞位点上，β-半乳糖苷酶表达的惊人缺乏与周围神经和神经肌肉接头的细胞结构的显著变化最为相关。在一些通常表达该分子的其他细胞位点（但不是全部），免疫荧光分析表明存在显著但低水平的腱生蛋白-C样免疫反应性以及β-半乳糖苷酶表达。通过逆转录聚合酶链反应检测信使核糖核酸证实骨骼肌中存在少量腱生蛋白-C信使核糖核酸，这表明缺乏腱生蛋白-C的小鼠并非该基因的完全敲除，而是低表达突变体。在体内注射A型肉毒杆菌毒素后，我们观察到腱生蛋白-C突变小鼠的运动神经发芽反应大大降低。我们还观察到N-CAM和β-连环蛋白在突变体中过度表达。我们的结果表明，腱生蛋白-C参与神经肌肉接头的稳定和可塑性。
