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The “CMT rat”: peripheral neuropathy and dysmyelination caused by transgenic overexpression of PMP22

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...

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Bibliographic Details
Main Authors: Niemann, Stephan (Author) , Sereda, Michael W. (Author) , Roßner, Moritz (Author) , Stewart, Helen (Author) , Suter, Ueli (Author) , Meinck, Hans-Michael (Author) , Griffiths, Ian R. (Author) , Nave, Klaus-Armin (Author)
Format: Article (Journal)
Language:English
Published: 1999
In: Annals of the New York Academy of Sciences
Year: 1999, Volume: 883, Pages: 254-261
ISSN:1749-6632
DOI:10.1111/j.1749-6632.1999.tb08587.x
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1111/j.1749-6632.1999.tb08587.x
Verlag, lizenzpflichtig, Volltext: https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.1999.tb08587.x
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Author Notes:Stephan Niemann, Michael W. Sereda, Moritz Rossner, Helen Stewart, Ueli Suter, Hans-Michael Meinck, Ian R. Griffiths, and Klaus-Armin Nave
Description
Summary: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.
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Physical Description:Online Resource
ISSN:1749-6632
DOI:10.1111/j.1749-6632.1999.tb08587.x

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