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Updated: Jun 2, 2026
In Vivo Electrophysiological Measurement of Compound Muscle Action Potential from the Forelimbs in Mouse Models of Motor Neuron Degeneration
Published on: June 15, 2018
Myelin and axon pathology in a long-term study of PMP22-overexpressing mice
Camiel Verhamme1, Rosalind H M King, Anneloor L M A ten Asbroek
1Department of Neurology and Clinical Neurophysiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. c.verhamme@amc.uva.nl
Abstract:
We analyzed clinical and pathological disease in 2 peripheral myelin protein-22 (PMP22) overexpressing mouse models for 1.5 years. C22 mice have 7 and C3-PMP mice have 3 to 4 copies of the human PMP22 gene. C3-PMP mice showed no overt clinical signs at 3 weeks and developed mild neuromuscular impairment; C22 mice showed signs at 3 weeks that progressed to severe impairment. Adult C3-PMP mice had very similar, stable, low nerve conduction velocities similar to adults with human Charcot-Marie-Tooth disease type 1A (CMT1A); velocities were much lower in C22 mice. Myelination was delayed, and normal myelination was not reached in either model but the degree of dysmyelination in C3-PMP mice was considerably less than that in C22 mice; myelination was stable in the adult mice. Numbers of myelinated, fibers were reduced at 3 weeks in both models, suggesting that normal numbers of myelinated fibers are not reached during development in the models. In adult C3-PMP and wild-type mice, there was no detectable loss of myelinated fibers,whereas there was clear loss of myelinated fibers in C22 mice.In C3-PMP mice, there is a balance between myelination status and axonal function early in life, whereas in C22 mice, early reduction of axons is more severe and there is major loss of axons in adulthood. We conclude that C3-PMP mice may be an appropriate model for most CMT1A patients, whereas C22 mice may be more relevant to severely affected patients in the CMT1 spectrum.
Insights
Two mouse models overexpressing peripheral myelin protein-22 (PMP22) were analyzed. C3-PMP mice offer a model for Charcot-Marie-Tooth disease type 1A (CMT1A), while C22 mice represent severe cases.
Area of Science:
- Neuroscience
- Genetics
- Pathology
Background:
- Peripheral myelin protein-22 (PMP22) gene duplications cause Charcot-Marie-Tooth disease type 1A (CMT1A).
- Mouse models are crucial for understanding PMP22-related neuropathies.
Purpose of the Study:
- To analyze clinical and pathological disease progression in two distinct PMP22 overexpressing mouse models.
- To evaluate their suitability as models for Charcot-Marie-Tooth disease type 1A (CMT1A).
Main Methods:
- Analysis of clinical signs and neuromuscular impairment over 1.5 years in C22 and C3-PMP mice.
- Assessment of nerve conduction velocities, myelination status, and fiber counts.
- Comparison of pathological findings with human CMT1A.
Main Results:
- C22 mice exhibited severe, progressive neuromuscular impairment, while C3-PMP mice showed mild impairment.
- C3-PMP mice displayed stable, low nerve conduction velocities similar to human CMT1A patients.
- Both models showed delayed myelination and reduced fiber numbers; C22 mice had significant axonal loss in adulthood.
Conclusions:
- The C3-PMP mouse model is suitable for studying typical Charcot-Marie-Tooth disease type 1A (CMT1A).
- The C22 mouse model may represent more severe forms of the CMT1 spectrum.
- These models provide valuable insights into PMP22-related neuropathies.
