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Axonal and neuromuscular synaptic phenotypes in WldS, SOD1G93A and ostes mutant mice identified by fiber-optic confocal microendoscopy
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Wong, Frances, Fan, Li, Wells, Sara, Hartley, Robert, Mackenzie, Francesca E., Oyebode, Oyinlola, Brown, Rosalind, Thomson, Derek, Coleman, Michael P. and Blanco, Gonzalo (2009) Axonal and neuromuscular synaptic phenotypes in WldS, SOD1G93A and ostes mutant mice identified by fiber-optic confocal microendoscopy. Molecular and Cellular Neuroscience, 42 (4). pp. 296-307. doi:10.1016/j.mcn.2009.08.002 ISSN 1044-7431.
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Official URL: http://dx.doi.org/10.1016/j.mcn.2009.08.002
Abstract
We used live imaging by fiber-optic confocal microendoscopy (CME) of yellow fluorescent protein (YFP) expression in motor neurons to observe and monitor axonal and neuromuscular synaptic phenotypes in mutant mice. First, we visualized slow degeneration of axons and motor nerve terminals at neuromuscular junctions following sciatic nerve injury in WldS mice with slow Wallerian degeneration. Protection of
axotomized motor nerve terminals was much weaker in WldS heterozygotes than in homozygotes. We then induced covert modifiers of axonal and synaptic degeneration in heterozygous WldS mice, by N-ethyl-Nnitrosourea (ENU) mutagenesis, and used CME to identify candidate mutants that either enhanced or
suppressed axonal or synaptic degeneration. From 219 of the F1 progeny of ENU-mutagenized BALB/c mice and thy1.2-YFP16/WldS mice, CME revealed six phenodeviants with suppression of synaptic degeneration.
Inheritance of synaptic protection was confirmed in three of these founders, with evidence of Mendelian inheritance of a dominant mutation in one of them (designated CEMOP_S5). We next applied CME repeatedly to living WldS mice and to SOD1G93A mice, an animal model of motor neuron disease, and observed degeneration of identified neuromuscular synapses over a 1–4 day period in both of these mutant lines. Finally, we used CME to observe slow axonal regeneration in the ENU-mutant ostes mouse strain. The
data show that CME can be used to monitor covert axonal and neuromuscular synaptic pathology and, when combined with mutagenesis, to identify genetic modifiers of its progression in vivo.
| Item Type: | Journal Article | ||||||
|---|---|---|---|---|---|---|---|
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences > Population, Evidence & Technologies (PET) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Journal or Publication Title: | Molecular and Cellular Neuroscience | ||||||
| Publisher: | Academic Press | ||||||
| ISSN: | 1044-7431 | ||||||
| Official Date: | November 2009 | ||||||
| Dates: |
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| Volume: | 42 | ||||||
| Number: | 4 | ||||||
| Page Range: | pp. 296-307 | ||||||
| DOI: | 10.1016/j.mcn.2009.08.002 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Access rights to Published version: | Restricted or Subscription Access |
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