Charcot-Marie Tooth (CMT) disease is a hereditary, demyelinating peripheral neuropathy, leading to progressive muscle atrophy, weakness and subsequent walking disabilities and sensory impairments. Charcot-Marie Tooth Type 1A (CMT1A) is the most common type of CMT, with a prevalence of 1-5/ 10,000 affected individuals worldwide. CMT1A is caused by a duplication of a segment on chromosome 17p11.2 containing the gene encoding peripheral myelin protein 22 (PMP22). PMP22 is essential for Schwann cell myelin development, membrane architecture and formation; leaving CMT1A patients with dysfunctional and prominent demyelinated nerve and axon fibers causing slow nerve conduction velocities.
To help accelerate CMT1A research to clinic, InnoSer offers specialized preclinical research services, using the C3-PMP22 mouse model of CMT1A. C3-PMP22 transgenic mice carry multiple copies of the wild-type human PMP22 gene. The C3-PMP22 model shows a mild disease phenotype that more resembles human disease, developing mild neuromuscular impairments in an age-dependent manner. At InnoSer, we performed extensive phenotyping analyses of C3-PMP22 mice (from 4 weeks to 15 weeks of age) including sciatic nerve conduction electrophysiology (nerve conduction velocity [NCV], and compound muscle action potential [CMAP]), and motor function (CatWalkTM, Balance Beam, grip strength, rotarod) (Figures 1-4). InnoSer’s team has also contributed to several publications using this model (Michailidou et al. 2023 and Prior et al. 2024).
C3-PMP22 mice show significant nerve conduction deficits
FIGURE 1. Representative electrophysiological trace in a 9-week-old C3-PMP22 mouse which is severely reduced compared to a WT.
FIGURE 2. Sciatic nerve conduction recording in C3-PMP22 mice. Compared to WT mice, C3-PMP22 mutant mice (9 weeks of age) show significantly prolonged nerve conduction velocity latencies, as well as a significant reduction in CMAP amplitude recordings.
C3–PMP22 mice display reduced motor function
FIGURE 4. Compared to WT mice, C3PMP22 mice (15 -week-old) show deficits in motor function as indicated by significantly (**P<0.01) lower RPMs reached per trial during the rotarod test.
Interested in performing efficacy studies together with InnoSer’s C3-PMP22 mouse model of CMT1A? Consulting with our neurology study experts will allow you to carry out tailored studies while collecting the most study-appropriate data.