The peripheral nerve and the neuromuscular junction are affected in the tenascin-C-deficient mouse

Cell Mol Biol (Noisy-le-grand). 1998 Mar;44(2):357-79.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / drug effects
  • Axons / pathology
  • Botulinum Toxins / pharmacology
  • Cell Adhesion Molecules, Neuronal / biosynthesis
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cytoskeletal Proteins / biosynthesis
  • Cytoskeletal Proteins / genetics
  • Female
  • Gene Expression Regulation
  • Genes, Reporter
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Neurologic Mutants
  • Motor Endplate / ultrastructure
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Neuromuscular Junction / metabolism
  • Neuromuscular Junction / ultrastructure*
  • Neuronal Plasticity
  • Peripheral Nerves / drug effects
  • Peripheral Nerves / metabolism
  • Peripheral Nerves / pathology*
  • Polymerase Chain Reaction
  • RNA, Messenger / biosynthesis
  • Sciatic Nerve / ultrastructure
  • Tenascin / biosynthesis
  • Tenascin / deficiency*
  • Tenascin / genetics
  • Tenascin / physiology
  • Trans-Activators*
  • Transgenes
  • beta Catenin
  • beta-Galactosidase / analysis

Substances

  • CTNNB1 protein, mouse
  • Cell Adhesion Molecules, Neuronal
  • Cytoskeletal Proteins
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Tenascin
  • Trans-Activators
  • beta Catenin
  • beta-Galactosidase
  • Botulinum Toxins