title: The peripheral nerve and the neuromuscular junction are affected in the tenascin-C-deficient mouse.
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.
authors.affiliation: Laboratoire Neuromodulations Interactives et Neuropathologies, INSERM, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Cifuentes-Diaz
authors.forename: E
authors.initials: E
authors.lastname: Velasco
authors.forename: F A
authors.initials: FA
authors.lastname: Meunier
authors.forename: D
authors.initials: D
authors.lastname: Goudou
authors.forename: L
authors.initials: L
authors.lastname: Belkadi
authors.forename: L
authors.initials: L
authors.lastname: Faille
authors.forename: M
authors.initials: M
authors.lastname: Murawsky
authors.forename: D
authors.initials: D
authors.lastname: Angaut-Petit
authors.forename: J
authors.initials: J
authors.lastname: Molgó
authors.forename: M
authors.initials: M
authors.lastname: Schachner
authors.forename: Y
authors.initials: Y
authors.lastname: Saga
authors.forename: S
authors.initials: S
authors.lastname: Aizawa
authors.forename: F
authors.initials: F
authors.lastname: Rieger
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D001905:Botulinum Toxins / Q000494:pharmacology; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D009045:Motor Endplate / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009469:Neuromuscular Junction / Q000378:metabolism / Q000648:ultrastructure*; D009473:Neuronal Plasticity; D010525:Peripheral Nerves / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D012584:Sciatic Nerve / Q000648:ultrastructure; D019063:Tenascin / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D015534:Trans-Activators; D019076:Transgenes; D051176:beta Catenin; D001616:beta-Galactosidase / Q000032:analysis
chemical_list: C495267:CTNNB1 protein, mouse; D015816:Cell Adhesion Molecules, Neuronal; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D019063:Tenascin; D015534:Trans-Activators; D051176:beta Catenin; D001616:beta-Galactosidase; D001905:Botulinum Toxins