CMT 1A Research from London

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(CMT 1A Research from London)

1: J Anat 2002 Apr;200(4):377-90

ABSTRACT:

Comparison of a new pmp22 transgenic mouse line with other mouse models

and human patients with CMT1A.

on AM, Perea J, McGuigan A, King RH, Muddle JR,

Gabreels-Festen AA, PK, Huxley C.

Division of Biomedical Sciences, and Clinical Sciences Centre, Imperial

College School of Science, Technology and Medicine, London, UK.

Charcot-Marie-Tooth disease type 1A is a dominantly inherited

demyelinating disorder of the peripheral nervous system. It is most

frequently caused by overexpression of peripheral myelin protein 22

(PMP22), but is also caused by point mutations in the PMP22 gene. We

describe a new transgenic mouse model (My41) carrying the mouse, rather

than the human, pmp22 gene. The My41 strain has a severe phenotype

consisting of unstable gait and weakness of the hind limbs that becomes

obvious during the first 3 weeks of life. My41 mice have a shortened

life span and breed poorly. Pathologically, My41 mice have a

demyelinating peripheral neuropathy in which 75% of axons do not

have a measurable amount of myelin. We compare the peripheral nerve

pathology seen in My41 mice, which carry the mouse pmp22 gene, with

previously described transgenic mice over-expressing the human PMP22

protein and Trembler-J (TrJ) mice which have a P16L substitution. We

also look at the differences between CMT1A duplication patients,

patients with the P16L mutation and their appropriate mouse models.