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Up-Regulation of MHC Class I Expression Accompanies but Is Not Required for Spontaneous Myopathy in Dysferlin-Deficient SJL/J Mice

https://doi.org/10.1016/S0002-9440(10)64906-1Get rights and content

We found that up-regulation of major histocompatibility complex (MHC) class I expression accompanies, but is not required for, appearance of spontaneous myopathy in SJL/J mice. In some neuromuscular diseases, MHC class I expression is markedly up-regulated in muscles, though the consequences of this up-regulation for pathology are not clear. To study MHC class I in myopathy, we compared muscles of SJL/J mice to muscles of SJL/J mice that were also MHC class I-deficient due to targeted mutation in the β-2-microglobulin gene (SJL/J B2m (−/−) mice). SJL/J mice show spontaneous myopathy and have a mutation in the dysferlin gene, a gene which is also mutated in human limb-girdle muscular dystrophy type 2B (LGMD2B). Muscles of eight-month-old SJL/J mice had higher levels of MHC class I expression than muscles of either C57BL/6J (wild-type) or SJL/J B2m (−/−) mice. In contrast, the percentage of abnormal muscle fibers was similar in SJL/J and SJL/J B2m (−/−) muscles. Invading Mac-1+ cells were most abundant in SJL/J B2m (−/−) muscles, moderately abundant in SJL/J muscles, and rare in C57BL/6J muscles. Thus, MHC class I was markedly up-regulated in SJL/J muscles, but this high level of MHC class I was not necessary for the appearance of myopathy.

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Supported by grants from National Institute of Arthritis and Musculoskeletal and Skin Diseases and the W. R. Hearst Fund of Harvard Medical School (to J. D.) and by grants from USDA (National Research Initiative Competitive Grants Program), National Institute of Dental and Craniofacial Research, National Heart, Lung, and Blood Institute, and the Muscular Dystrophy Association (to J. B. M.).

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