Neuromuscular junction defects in mice with mutation of dynein heavy chain 1
| Autor: | Maria F. Pazyra-Murphy, Daniel J. Lee, Stephanie L. Courchesne, Rosalind A. Segal |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Cytoplasmic Dyneins
Anatomy and Physiology Mouse Science Dynein Neuromuscular Junction Neurophysiology Hindlimb Biology medicine.disease_cause Neuromuscular junction Neurological System Motor Neuron Diseases 03 medical and health sciences Mice 0302 clinical medicine Model Organisms Developmental Neuroscience Neurobiology of Disease and Regeneration medicine Animals 030304 developmental biology Motor Systems 0303 health sciences Mutation Multidisciplinary Synapse assembly Behavior Animal Neurodegenerative Diseases Anatomy Animal Models Motor neuron Sensory neuron Axons Cell biology medicine.anatomical_structure Phenotype Neurology Synapses Axoplasmic transport Medicine Molecular Neuroscience 030217 neurology & neurosurgery Research Article Neuroscience |
| Zdroj: | PLoS ONE, Vol 6, Iss 2, p e16753 (2011) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Disruptions in axonal transport have been implicated in a wide range of neurodegenerative diseases. Cramping 1 (Cra1/+) and Legs at odd angles (Loa/+) mice, with hypomorphic mutations in the dynein heavy chain 1 gene, which encodes the ATPase of the retrograde motor protein dynein, were originally reported to exhibit late onset motor neuron disease. Subsequent, conflicting reports suggested that sensory neuron disease without motor neuron loss underlies the phenotypes of Cra1/+ and Loa/+ mice. Here, we present behavioral and anatomical analyses of Cra1/+ mice. We demonstrate that Cra1/+ mice exhibit early onset, stable behavioral deficits, including abnormal hindlimb posturing and decreased grip strength. These deficits do not progress through 24 months of age. No significant loss of primary motor neurons or dorsal root ganglia sensory neurons was observed at ages where the mice exhibited clear symptomatology. Instead, there is a decrease in complexity of neuromuscular junctions. These results indicate that disruption of dynein function in Cra1/+ mice results in abnormal morphology of neuromuscular junctions. The time course of behavioral deficits, as well as the nature of the morphological defects in neuromuscular junctions, suggests that disruption of dynein function in Cra1/+ mice causes a developmental defect in synapse assembly or stabilization. |
| Databáze: | OpenAIRE |
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