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Journal Article

The “CMT Rat”: Peripheral Neuropathy and Dysmyelination Caused by Transgenic Overexpression ofPMP22

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Nave,  K.-A.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

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Citation

Niemann, S., Sereda, M. W., Rossner, M., Stewart, H., Suter, U., Meinck, H.-M., et al. (1999). The “CMT Rat”: Peripheral Neuropathy and Dysmyelination Caused by Transgenic Overexpression ofPMP22. Annals of the New York Academy of Sciences, 883(1), 254-261. doi:10.1111/j.1749-6632.1999.tb08587.x.


Cite as: https://hdl.handle.net/21.11116/0000-000D-2C53-5
Abstract
We have generated a transgenic rat model of Charcot-Marie-Tooth disease type 1A (CMT1A) providing formal proof that this neuropathy can be caused by increased expression of peripheral myelin protein-22 (PMP22). Heterozygous PMP22-transgenic rats develop muscle weakness and gait abnormalities as well as reduced nerve conduction velocities and EMG abnormalities, which closely resemble recordings in patients with CMT1A. Dys- and demyelination, Schwann cell hypertrophy, and “onion bulb” formation are also similar to findings in humans. When bred to homozygosity, transgenic rats completely fail to elaborate myelin, but all myelin-forming Schwann cells segregate with axons in the normal one-to-one ratio. Although arrested at this “promyelin” stage, differentiation proceeds in homozygous rats at the molecular level, as demonstrated by high-level expression of myelin structural genes. Intracellular trafficking of the wild-type protein is not visibly impaired, even when strongly overexpressed, suggesting that PMP22 blocks myelin assembly in a late Golgi/cell membrane compartment of the affected Schwann cell.