Trembler mouse carries a point mutation in a myelin gene (original) (raw)

Nature volume 356, pages 241–244 (1992)Cite this article

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 life5,6. 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).

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Author notes

  1. Andrew A. Welcher
    Present address: Amgen Inc., Thousand Oaks, California, 91320, USA

Authors and Affiliations

  1. Department of Neurobiology, Stanford University School of Medicine, Stanford, California, 94305, USA
    Ueli Suter, Andrew A. Welcher, G. Jackson Snipes & Eric M. Shooter
  2. Department of Neuropathology, Stanford University School of Medicine, Stanford, California, 94305, USA
    G. Jackson Snipes
  3. Department of Genetics and Pediatrics, Stanford University School of Medicine, Stanford, California, 94305, USA
    Uta Francke
  4. Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, 94305, USA
    Tayfun Özcelik & Uta Francke
  5. Division of Neurogenetics, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts, 01772, USA
    Bela Kosaras & Richard L. Sidman
  6. Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts, 01605, USA
    Susan Billings-Gagliardi

Authors

  1. Ueli Suter
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  2. Andrew A. Welcher
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  3. Tayfun Özcelik
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  4. G. Jackson Snipes
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  5. Bela Kosaras
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  6. Uta Francke
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  7. Susan Billings-Gagliardi
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  8. Richard L. Sidman
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  9. Eric M. Shooter
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Suter, U., Welcher, A., Özcelik, T. et al. Trembler mouse carries a point mutation in a myelin gene.Nature 356, 241–244 (1992). https://doi.org/10.1038/356241a0

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