title: Myotonic dystrophy transgenic mice exhibit pathologic abnormalities in diaphragm neuromuscular junctions and phrenic nerves.
abstract: Myotonic dystrophy Type 1 (DM-1) is caused by abnormal expansion of a (CTG) repeat located in the DM protein kinase gene. Respiratory problems have long been recognized to be a major feature of this disorder. Because respiratory failure can be associated with dysfunction of phrenic nerves and diaphragm muscle, we examined the diaphragm and respiratory neural network in transgenic mice carrying the human genomic DM-1 region with expanded repeats of more than 300 CTG, a valid model of the human disease. Morphologic and morphometric analyses revealed distal denervation of diaphragm neuromuscular junctions in DM-1 transgenic mice indicated by a decrease in the size and shape complexity of end-plates and a reduction in the concentration of acetyl choline receptors on the postsynaptic membrane. More importantly, there was a significant reduction in numbers of unmyelinated, but not of myelinated, fibers in DM-1 phrenic nerves; no morphologic alternations of the nerves or loss of neuronal cells were detected in medullary respiratory centers or cervical phrenic motor neurons. Because neuromuscular junctions are involved in action potential transmission and the afferent phrenic unmyelinated fibers control the inspiratory activity, our results suggest that the respiratory impairment associated with DM-1 may be partially due to pathologic alterations in neuromuscular junctions and phrenic nerves.
authors.affiliation: Neurology Service, Centre Hospitalier Universitaire Vaudois, Switzerland.
authors.forename: Petrica-Adrian
authors.initials: PA
authors.lastname: Panaite
authors.forename: Emilien
authors.initials: E
authors.lastname: Gantelet
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kraftsik
authors.forename: Geneviève
authors.initials: G
authors.lastname: Gourdon
authors.forename: Thierry
authors.initials: T
authors.lastname: Kuntzer
authors.forename: Ibtissam
authors.initials: I
authors.lastname: Barakat-Walter
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D002038:Bungarotoxins / Q000378:metabolism; D003964:Diaphragm / Q000473:pathology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000473:pathology; D009223:Myotonic Dystrophy / Q000235:genetics* / Q000473:pathology*; D016900:Neurofilament Proteins / Q000378:metabolism; D009469:Neuromuscular Junction / Q000473:pathology*; D010791:Phrenic Nerve / Q000473:pathology*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
chemical_list: D002038:Bungarotoxins; D016900:Neurofilament Proteins