Human Molecular Genetics, Vol 7, 449-458, Copyright © 1998 by Oxford University Press
C Huxley, E Passage, AM Robertson, B Youl, S Huston, A Manson, D Saberan- Djoniedi, D Figarella-Branger, JF Pellissier, PK Thomas and M Fontes
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 approximately 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.
ARTICLES
Correlation between varying levels of PMP22 expression and the degree of demyelination and reduction in nerve conduction velocity in transgenic mice
Imperial College School of Medicine at St Mary's, London W2 1PG, UK. c.huxley@ic.ac.uk
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