Help Privacy Policy Disclaimer
  Advanced SearchBrowse




Journal Article

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


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

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available

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
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.