Journal Article

Correlation Between Varying Levels of PMP22 Expression and the Degree of Demyelination and Reduction in Nerve Conduction Velocity in Transgenic Mice

C. Huxley, E. Passage, A. M. Robertson, B. Youl, S. Huston, A. Manson, D. Sabéran-Djoniedi, D. Figarella-Branger, J. F. Pellissier, P. K. Thomas and M. Fontés

in Human Molecular Genetics

Volume 7, issue 3, pages 449-458
Published in print March 1998 | ISSN: 0964-6906
Published online March 1998 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/7.3.449
Correlation Between Varying Levels of PMP22 Expression and the Degree of Demyelination and Reduction in Nerve Conduction Velocity in Transgenic Mice

Show Summary Details

Preview

Charcot-Marie-Tooth disease type 1A is most commonly caused by a duplication of a 1.5 Mb region of chromosome 17 which includes the peripheral myelin protein 22 gene (PMP22). Over-expression of this gene leads to a hypomyelinating/demyelinating neuropathy and to severely reduced nerve conduction velocity. Previous mouse and rat models have had relatively high levels of expression of the mouse or human PMP22 gene leading to severe demyelination. Here we describe five lines of transgenic mice carrying increasing copies of the human PMP22 gene (one to seven) and expressing increasing levels of the transgene. From histological and electrophysiological observations there appears to be a threshold below which expression of PMP22 has virtually no effect; below a ratio of human/mouse mRNA expression of ∼0.8, little effect is observed. Between a ratio of 0.8 and 1.5, histological and nerve conduction velocity abnormalities are observed, but there are no behavioural signs of neuropathy. An expression ratio >1.5 leads to a severe neuropathy. A second observation concerns the histology of the different lines; the level of expression does not affect the type of demyelination, but influences the severity of involvement.

Journal Article.  5965 words.  Illustrated.

Subjects: Genetics and Genomics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.