Molecular and cellular neurosciences
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Mol. Cell. Neurosci. · Dec 2009
Axonal and neuromuscular synaptic phenotypes in Wld(S), SOD1(G93A) and ostes mutant mice identified by fiber-optic confocal microendoscopy.
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 Wld(S) mice with slow Wallerian degeneration. Protection of axotomized motor nerve terminals was much weaker in Wld(S) heterozygotes than in homozygotes. ⋯ We next applied CME repeatedly to living Wld(S) mice and to SOD1(G93A) mice, an animal model of motor neuron disease, and observed degeneration of identified neuromuscular synapses over a 1-4day 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.