Analysis Tools
nervous system
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• uninjured mutant mice exhibit severe anatomical defects in the peripheral nervous system
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• significantly increased number of dystrophic swellings observed in foot pad intraepidermal sensory nerve fibers relative to wild-type controls
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• large dystrophic swellings are observed in presynaptic terminals with virtual absence of postsynaptic receptor expression
• severe decline in the acetylcholine receptor apposition of presynaptic terminals, with ~50% of synapses showing less than half of their presynaptic area opposed by acetylcholine receptors
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• severe morphological defects in neuromuscular junctions (NMJs) formed at the extensor hallucis longus (EHL) muscle at 8-10 weeks of age
• large dystrophic swellings in presynaptic terminals as well as in synapses onto the tibialis anterior and diaphragm muscles, suggesting a generalized defect in NMJ architecture
• frequency of swellings is significantly increased at 2-3 and 6.5 months of age, suggesting a progressive neurodegenerative disease
• however, no severe postsynaptic defect is detected at the NMJ
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• frequency of synaptic swellings at NMJs increases significantly with age, suggesting a progressive neurodegeneration disease
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• brief but significant delay in axon degeneration following sciatic nerve injury, with ~6 times the number of intact myelinated axons remaining at 3 days post-injury but comparable axon loss at 5 days post-injury relative to wild-type controls
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• mice display deficits in sensory-motor function, consistent with structural anomalies found at sensory and motor terminals
• however, action potential amplitudes and conduction velocities in both sensory and motor nerves are normal
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behavior/neurological
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• mice hold on to an inverted screen for significantly less time than wild-type controls
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cellular
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• electron microscopy of NMJs on the EHL muscle revealed swollen presynaptic terminals with membranous aggregates
• abnormal vesicular structures are found near the EHL muscle fiber surface; some aggregates are surrounded by a double membrane typical of autophagosomes
• in skeletal muscle (tibialis anterior), occasional myofibers show abnormal accumulations of autophagosomes and/or lysosomes in their center
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muscle
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• in skeletal muscle (tibialis anterior), occasional myofibers show abnormal accumulations of autophagosomes and/or lysosomes in their center
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homeostasis/metabolism
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• electron microscopy of NMJs on the EHL muscle revealed swollen presynaptic terminals with membranous aggregates
• abnormal vesicular structures are found near the EHL muscle fiber surface; some aggregates are surrounded by a double membrane typical of autophagosomes
• in skeletal muscle (tibialis anterior), occasional myofibers show abnormal accumulations of autophagosomes and/or lysosomes in their center
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