Trembler mouse carries a point mutation in a myelin gene

Abstract

THE autosomal dominant trembler mutation¹ (Tr), maps to mouse chromosome 11 (ref. 2) and manifests as a Schwann-cell defect³characterized by severe hypomyelination⁴ 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–Tooth⁹ and Dejerine–Sottas¹⁰ diseases (hereditary motor and sensory neuropathies I and III).