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. 1980 Sep 1;152(3):507–520. doi: 10.1084/jem.152.3.507

Linkage between the frequency of muscular weakness and loci that regulate immune responsiveness in murine experimental myasthenia gravis

PMCID: PMC2185932  PMID: 6774045

Abstract

Mice immunized with acetylcholine receptor (AChR) purified from Torpedo californica form anti-AChR antibodies and often develop muscular weakness and flaccid paralysis closely resembling the human disease myasthenia gravis. This condition, termed experimental myasthenia gravis (EMG), is strain dependent in that the frequency of paralysis is much greater in some strains than in others. Differences in the frequency of EMG might result from differences in the immune system or the neuromuscular junction. In these studies, we have identified two loci, the major histocompatibility complex (H-2) region on chromosome 17 and the region that contains the structural genes for the constant region of immunoglobulin heavy chains (IgCH region) on chromosome 12, which significantly effect the probability with which a mouse immunized with T. californica AChR can be expected to become paralyzed. One genotype (H-2b, Ig-1b) correlated with high susceptibility to EMG in four strains with three dissimilar backgrounds. These studies demonstrate that susceptibility to EMG is a heritable trait determined by at least two distinct loci that are linked to regions of the mouse genome that regulate immune responsiveness.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Appel S. H., Almon R. R., Levy N. Acetylcholine receptor antibodies in myasthenia gravis. N Engl J Med. 1975 Oct 9;293(15):760–761. doi: 10.1056/NEJM197510092931508. [DOI] [PubMed] [Google Scholar]
  2. Benacerraf B., Germain R. N. The immune response genes of the major histocompatibility complex. Immunol Rev. 1978;38:70–119. doi: 10.1111/j.1600-065x.1978.tb00385.x. [DOI] [PubMed] [Google Scholar]
  3. Berman P. W., Patrick J. Experimental myasthenia gravis. A murine system. J Exp Med. 1980 Jan 1;151(1):204–223. doi: 10.1084/jem.151.1.204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blomberg B., Geckeler W. R., Weigert M. Genetics of the antibody response to dextran in mice. Science. 1972 Jul 14;177(4044):178–180. doi: 10.1126/science.177.4044.178. [DOI] [PubMed] [Google Scholar]
  5. Christadoss P., Lennon V. A., David C. Genetic control of experimental autoimmune myasthenia gravis in mice. I. Lymphocyte proliferative response to acetylcholine receptors is under H-2-linked Ir gene control. J Immunol. 1979 Dec;123(6):2540–2543. [PubMed] [Google Scholar]
  6. Claflin J. L., Wolfe J., Ruppert V. J. Structural evidence for recombination at the Igh (H chain) complex locus in BAB 14 mice. J Immunol. 1979 Nov;123(5):2088–2090. [PubMed] [Google Scholar]
  7. Drachman D. B. Myasthenia gravis (second of two parts). N Engl J Med. 1978 Jan 26;298(4):186–193. doi: 10.1056/NEJM197801262980404. [DOI] [PubMed] [Google Scholar]
  8. Fuchs S., Nevo D., Tarrab-Hazdai R., Yaar I. Strain differences in the autoimmune response of mice to acetylcholine receptors. Nature. 1976 Sep 23;263(5575):329–330. doi: 10.1038/263329a0. [DOI] [PubMed] [Google Scholar]
  9. Fulpius B. W., Zurn A. D., Granato D. A., Leder R. M. Acetylcholine receptor and myasthenia gravis. Ann N Y Acad Sci. 1976;274:116–129. doi: 10.1111/j.1749-6632.1976.tb47680.x. [DOI] [PubMed] [Google Scholar]
  10. Geckeler W., Blomberg B., de Preval C., Cohn M. On the genetic dissection of a specific humoral immune response to alpha(1,3) dextran. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 2):743–748. doi: 10.1101/sqb.1977.041.01.085. [DOI] [PubMed] [Google Scholar]
  11. Lefvert A. K., Bergström K., Matell G., Osterman P. O., Pirskanen R. Determination of acetylcholine receptor antibody in myasthenia gravis: clinical usefulness and pathogenetic implications. J Neurol Neurosurg Psychiatry. 1978 May;41(5):394–403. doi: 10.1136/jnnp.41.5.394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lindstrom J. M., Seybold M. E., Lennon V. A., Whittingham S., Duane D. D. Antibody to acetylcholine receptor in myasthenia gravis. Prevalence, clinical correlates, and diagnostic value. Neurology. 1976 Nov;26(11):1054–1059. doi: 10.1212/wnl.26.11.1054. [DOI] [PubMed] [Google Scholar]
  13. Lindstrom J. Autoimmune response to acetylcholine receptors in myasthenia gravis and its animal model. Adv Immunol. 1979;27:1–50. doi: 10.1016/s0065-2776(08)60261-8. [DOI] [PubMed] [Google Scholar]
  14. Meo T., Johnson J., Beechey C. V., Andrews S. J., Peters J., Searle A. G. Linkage analyses of murine immunoglobulin heavy chain and serum prealbumin genes establish their location on chromosome 12 proximal to the T (5;12) 31H breakpoint in band 12F1. Proc Natl Acad Sci U S A. 1980 Jan;77(1):550–553. doi: 10.1073/pnas.77.1.550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Patrick J., Lindstrom J. Autoimmune response to acetylcholine receptor. Science. 1973 May 25;180(4088):871–872. doi: 10.1126/science.180.4088.871. [DOI] [PubMed] [Google Scholar]
  16. Pisetsky D. S., Riordan S. E., Sachs D. H. Genetic control of the immune response to staphylococcal nuclease. IX. Recombination between genes determining BALB/c antinuclease idiotypes and the heavy chain allotype locus. J Immunol. 1979 Mar;122(3):842–846. [PubMed] [Google Scholar]
  17. Riblet R., Weigert M., Mäkelä O. Genetics of mouse antibodies. II. Recombination between VH genes and allotype. Eur J Immunol. 1975 Nov;5(11):778–781. doi: 10.1002/eji.1830051110. [DOI] [PubMed] [Google Scholar]
  18. Shreffler D. C., David C. S. The H-2 major histocompatibility complex and the I immune response region: genetic variation, function, and organization. Adv Immunol. 1975;20:125–195. doi: 10.1016/s0065-2776(08)60208-4. [DOI] [PubMed] [Google Scholar]

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