TREMBLER MOUSE CARRIES A POINT MUTATION IN A MYELIN GENE

THE autosomal dominant trembler mutation 1 (Tr), maps to mouse chromosome 11 (ref. 2) and manifests as a Schwann-cell defect 3 characterized by severe hypomyelination 4 and continuing Schwann-cell proliferation throughout life 5,6. Affected animals move clumsily and develop tremor and transient seizures at a young age. We have recently described a potentially growth-regulating myelin protein, peripheral myelin protein-22 (PMP-22; refs 7,8), which is expressed by Schwann cells and found in peripheral myelin. We now report the assignment of the gene for PMP-22 to mouse chromosome 11. Cloning and sequencing of PMP-22 complementary DNAs from inbred Tr mice reveals a point mutation that substitutes an aspartic acid residue for a glycine in a putative membrane-associated domain of the PMP-22 protein. Our results identify the PMP-22 gene as a likely candidate for the mouse trembler locus and will encourage the search for mutations in the corresponding human gene in pedigrees with hypertrophic neuropathies such as Charcot-Marie-Tooth 9 and Dejerine-Sottas 10 diseases (hereditary motor and sensory neuropathies I and III).