Trembler mouse carries a point mutation in a myelin gene.
The autosomal dominant trembler mutation (Tr), maps to mouse chromosome 11 (ref. 2) and manifests as a Schwann-cell defect characterized by severe hypomyelination and continuing Schwann-cell proliferation throughout life. 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 and Dejerine-Sottas diseases (hereditary motor and sensory neuropathies I and III).
Suter
U
U
Department of Neurobiology, Stanford University School of Medicine, California 94305.
Welcher
A A
AA
Ozcelik
T
T
Snipes
G J
GJ
Kosaras
B
B
Francke
U
U
Billings-Gagliardi
S
S
Sidman
R L
RL
Shooter
E M
EM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification; D015870:Gene Expression; D051379:Mice; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D009185:Myelin Proteins / Q000737:chemistry / Q000235:genetics*; D009186:Myelin Sheath / Q000502:physiology*; D009422:Nervous System Diseases / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012583:Schwann Cells / Q000378:metabolism
D009185:Myelin Proteins; C489545:Pmp22 protein, mouse; D004247:DNA