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Neuromuscular Junction Defects in Mice with Mutation of dynein heavy chain 1

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 r...

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Autores principales: Courchesne, Stephanie L., Pazyra-Murphy, Maria F., Lee, Daniel J., Segal, Rosalind A.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3035627/
https://www.ncbi.nlm.nih.gov/pubmed/21346813
http://dx.doi.org/10.1371/journal.pone.0016753
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author Courchesne, Stephanie L.
Pazyra-Murphy, Maria F.
Lee, Daniel J.
Segal, Rosalind A.
author_facet Courchesne, Stephanie L.
Pazyra-Murphy, Maria F.
Lee, Daniel J.
Segal, Rosalind A.
author_sort Courchesne, Stephanie L.
collection PubMed
description 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.
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spelling pubmed-30356272011-02-23 Neuromuscular Junction Defects in Mice with Mutation of dynein heavy chain 1 Courchesne, Stephanie L. Pazyra-Murphy, Maria F. Lee, Daniel J. Segal, Rosalind A. PLoS One Research Article 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. Public Library of Science 2011-02-04 /pmc/articles/PMC3035627/ /pubmed/21346813 http://dx.doi.org/10.1371/journal.pone.0016753 Text en This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Courchesne, Stephanie L.
Pazyra-Murphy, Maria F.
Lee, Daniel J.
Segal, Rosalind A.
Neuromuscular Junction Defects in Mice with Mutation of dynein heavy chain 1
title Neuromuscular Junction Defects in Mice with Mutation of dynein heavy chain 1
title_full Neuromuscular Junction Defects in Mice with Mutation of dynein heavy chain 1
title_fullStr Neuromuscular Junction Defects in Mice with Mutation of dynein heavy chain 1
title_full_unstemmed Neuromuscular Junction Defects in Mice with Mutation of dynein heavy chain 1
title_short Neuromuscular Junction Defects in Mice with Mutation of dynein heavy chain 1
title_sort neuromuscular junction defects in mice with mutation of dynein heavy chain 1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3035627/
https://www.ncbi.nlm.nih.gov/pubmed/21346813
http://dx.doi.org/10.1371/journal.pone.0016753
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