PMP22 mutant mouse models of CMT peripheral neuropathy

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 weak-
ness 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.
Key words myelin; neuropathy; PMP22; Trembler-J mouse.