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Absence of neurological deficits following extensive demyelination in a class I-deficient murine model of multiple sclerosis

Nature Medicine volume 4, pages 187–193 (1998)Cite this article

Abstract

Demyelination alone has been considered sufficient for development of neurological deficits following central nervous system (CNS) disease. However, extensive demyelination is not always associated with clinical deficits in patients with multiple sclerosis (MS), the most common primary demyelinating disease in humans. We used the Theiler's murine encephalomyelitis virus model of demyelination to investigate the role of major histocompatibility complex (MHC) class I and class II gene products In the development of functional and neurophysiological deficits following demyelination. We measured spontaneous clinical activity by two independent assays and recorded hind-limb motor-evoked potentials in infected class I-deficient and class 11-deficient mice of an identical genetic background as well as in highly susceptible SJL/J mice. The results show that despite a similar distribution and extent of demyelinated lesions in all mice, only class I-deficient mice were functionally normal. We propose that the mechanism by which demyelinated class I-deficient mice maintain neurologic function results from increased sodium channel densities and the relative preservation of axons. These findings are the first to implicate a role for MHC class I in the development of neurological deficits following demyelination.

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Authors and Affiliations

  1. Department of Neurology, Mayo Clinic and Foundation, 200 First Street SW, Rochester, Minnesota, 55905, USA

    Cynthia Rivera-Quiñones, James D. Schmelzer, Samuel F. Hunter, Phillip A. Low & Moses Rodriguez

  2. Department of Immunology, Mayo Clinic and Foundation, 200 First Street SW, Rochester, Minnesota, 55905, USA

    Cynthia Rivera-Quiñones & Moses Rodriguez

  3. Molecular Neuroscience Program, Mayo Clinic and Foundation, 200 First Street SW, Rochester, Minnesota, 55905, USA

    Dorian McGavern & Moses Rodriguez

Authors
  1. Cynthia Rivera-Quiñones
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  2. Dorian McGavern
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  3. James D. Schmelzer
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  4. Samuel F. Hunter
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  5. Phillip A. Low
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  6. Moses Rodriguez
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Rivera-Quiñones, C., McGavern, D., Schmelzer, J. et al. Absence of neurological deficits following extensive demyelination in a class I-deficient murine model of multiple sclerosis. Nat Med 4, 187–193 (1998). https://doi.org/10.1038/nm0298-187

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