Analysis Tools
behavior/neurological
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• mutants occasionally self-mutilate their tails which may be possible evidence of paresthesia
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• mutants perform worse than controls in the tail-flick test indicating impaired sensory function
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• mutants show abnormal clenching of toes and clasping of hind limbs upon tail suspension at 1 year of age, with some flexing all four limbs and even their whole body
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• mutants show impaired motor performance after the 4th trial of the rotarod test
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nervous system
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• axon contours of sciatic nerves are less circular and axon caliber and axon area are smaller than in controls
• axons with myelin infoldings are often displaced, deformed, or constricted
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• segregation of the paranodal and juxtaparanodal compartments is disrupted in axons, with 73% of nodes of Ranvier in sciatic nerves having a paranode-juxtaparanode overlap phenotype
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• 1 year old mutants exhibit peripheral nerves with abnormal Schwann cell-axon units with focally infolded myelin sheaths that appear as single, double, or triple internal myelin rings within a myelinated axon
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• nodes of Ranvier with myelin infolding often show paranodal retraction leading to a larger nodal gap
• nodal gap length of sciatic nerves is longer than in controls
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• segregation of the paranodal and juxtaparanodal compartments is disrupted in axons, with 73% of nodes of Ranvier in sciatic nerves having a paranode-juxtaparanode overlap phenotype
• accumulation of electron-dense organelles, mainly mitochondria, in the axoplasm of the paranodal region next to the infolded myelin
• presence of myelin infoldings at the paranodal regions and these regions often show signs of dys/demyelination and axonal damage
• non-compacted myelin whorls extend from the compact myelin into the axon, suggesting loss of myelin compaction at the paranodal region
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• sciatic nerves from 12-15 month old mutants exhibit abundant myelin abnormalities with focally folded structures
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• small but significant increase in the percentage of sciatic nerves undergoing axonal degeneration at 12-15 months of age
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• peripheral nerve dysmyelination with myelin infolding
• myelin infolding is specific to peripheral nerves and is seen in motor and sensory nerves; infoldings are more prominent in sciatic nerves than in ventral or dorsal roots
• infolded myelin loops originate from the myelin sheath at the paranodal regions and the internodal regions adjacent to Schmidt-Lanterman incisures
• occasionally, loss of myelin compaction and widened spacing of the Schmidt-Lanterman incisures are seen
• non-compacted myelin whorls extend from the compact myelin into the axon, suggesting loss of myelin compaction at the paranodal region
• myelin infoldings precede axonal defects (nodal disorganization) in sciatic nerves
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• small but significant increase in the percentage of sciatic nerves with demyelinated axons at 12-15 months of age
• paranodal regions with myelin infolding often show signs of dys/demyelination and axonal damage
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• compound muscle action potential amplitudes are reduced at 1 year of age, but not at 3 months
• sensory nerve action potentials could not be evoked in 2 of 11 mutants
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• motor nerve and tail sensory nerve conduction velocity are reduced at 1 year of age, but not 3 months of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Charcot-Marie-Tooth disease type 1C | DOID:0110151 |
OMIM:601098 |
J:194981 | |
