A TRANSGENIC RAT MODEL OF CHARCOT-MARIE-TOOTH DISEASE

Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropa thy in humans and has been associated with a partial duplication of ch romosome 17 (CMT type 1A). We have generated a transgenic rat model of this disease and provide experimental evidence that CMT1A is caused b y increased expression of the gene for peripheral myelin protein-22 (P MP22, gas-3). PMP22-transgenic rats develop gait abnormalities caused by a peripheral hypomyelination, Schwann cell hypertrophy (onion bulb formation), and muscle weakness. Reduced nerve conduction velocities c losely resemble recordings in human patients with CMT1A. When bred to homozygosity, transgenic animals completely fail to elaborate myelin. We anticipate that the CMT rat model will facilitate the identificatio n of a cellular disease mechanism and serve in the evaluation of poten tial treatment strategies.