title: Up-regulation of MHC class I expression accompanies but is not required for spontaneous myopathy in dysferlin-deficient SJL/J mice.
abstract: 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 beta-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.
authors.affiliation: Boston Biomedical Research Institute, Watertown, MA 02478, USA.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Kostek
authors.forename: Janice A
authors.initials: JA
authors.lastname: Dominov
authors.forename: Jeffrey Boone
authors.initials: JB
authors.lastname: Miller
mesh_terms: D000818:Animals; D000073939:Dysferlin; D017353:Gene Deletion; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics*; D009136:Muscular Dystrophies / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C114839:DYSF protein, human; D000073939:Dysferlin; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D009124:Muscle Proteins