title: Nerve and muscle development in paralysé mutant mice.
abstract: Nerve and muscle development was studied in paralysé mutant mice. The mutant phenotype is first recognizable 6-7 days after birth (PN 6-PN 7) as cessation of muscle growth and weakness and incoordination of movement. Mutant animals die between 2 and 3 weeks of age. Muscle fibers from paralysé mutants had a unimodal distribution of diameters and normal numbers and distributions of acetylcholine receptors. The only structural abnormality seen was a reduced extracellular space within muscle fascicles. Total muscle choline acetyltransferase activity was reduced compared with that of control muscles, indicating that synaptic terminal development was impaired. Light and electron microscopy showed that polyneuronal innervation was retained in mutant endplates, and the normal process of withdrawal of redundant innervation did not occur. The paralysé muscles reacted to experimental denervation with an increase in extrajunctional acetylcholine receptor numbers. Intramuscular axons failed to become myelinated in mutant animals, although sciatic nerve axons were myelinated with a normal myelin thickness/axon diameter ratio. Nodes of Ranvier were elongated and myelin lamellae in the paranodal regions were poorly fused. Sciatic nerves in mutant animals retained the neonatal unimodal distribution of axon diameters, whereas in control animals it became bimodal by 2 weeks of age. Our results are not consistent with a previous suggestion that paralysé mutant muscle endplates are progressively denervated. We conclude that the major expression of the paralysé mutant phenotype is an arrest in development of both nerve and muscle during the first week after birth. The paralysé mutant gene most likely is involved in the general support of development of many or all body tissues from 1 week of age. We found no regression of any aspect of differentiation, once achieved.
authors.affiliation: INSERM U. 153, Biologie et Pathologie Neuromuscularies, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Blondet
authors.forename: M J
authors.initials: MJ
authors.lastname: Duxson
authors.forename: A J
authors.initials: AJ
authors.lastname: Harris
authors.forename: J
authors.initials: J
authors.lastname: Melki
authors.forename: J L
authors.initials: JL
authors.lastname: Guénet
authors.forename: M
authors.initials: M
authors.lastname: Pinçon-Raymond
authors.forename: F
authors.initials: F
authors.lastname: Rieger
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000648:ultrastructure; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains / Q000254:growth & development*; D008854:Microscopy, Electron; D009046:Motor Neurons / Q000502:physiology; D009121:Muscle Denervation; D024510:Muscle Development; D009124:Muscle Proteins / Q000502:physiology; D009132:Muscles / Q000648:ultrastructure; D009186:Myelin Sheath / Q000502:physiology; D009411:Nerve Endings / Q000502:physiology; D009420:Nervous System / Q000254:growth & development*; D011950:Receptors, Cholinergic / Q000502:physiology
chemical_list: D009124:Muscle Proteins; D011950:Receptors, Cholinergic; D002795:Choline O-Acetyltransferase