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Upregulation of MHC class I in transgenic mice results in reduced force‐generating capacity in slow‐twitch muscle
Author(s) -
Salomonsson Stina,
Grundtman Cecilia,
Zhang ShiJin,
Lanner Johanna T.,
Li Charles,
Katz Abram,
Wedderburn Lucy R.,
Nagaraju Kanneboyina,
Lundberg Ingrid E.,
Westerblad Håkan
Publication year - 2009
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.21129
Subject(s) - skeletal muscle , major histocompatibility complex , soleus muscle , muscle weakness , mhc class i , extensor digitorum longus muscle , transgene , endocrinology , medicine , inflammation , muscle atrophy , genetically modified mouse , myopathy , biology , atrophy , muscle stiffness , mhc class ii , downregulation and upregulation , anatomy , immunology , gene , immune system , biochemistry , stiffness , structural engineering , engineering
Expression of major histocompatibility complex (MHC) class I in skeletal muscle fibers is an early and consistent finding in inflammatory myopathies. To test if MHC class I has a primary role in muscle impairment, we used transgenic mice with inducible overexpression of MHC class I in their skeletal muscle cells. Contractile function was studied in isolated extensor digitorum longus (EDL, fast‐twitch) and soleus (slow‐twitch) muscles. We found that EDL was smaller, whereas soleus muscle was slightly larger. Both muscles generated less absolute force in myopathic compared with control mice; however, when force was expressed per cross‐sectional area, only soleus muscle generated less force. Inflammation was markedly increased, but no changes were found in the activities of key mitochondrial and glycogenolytic enzymes in myopathic mice. The induction of MHC class I results in muscle atrophy and an intrinsic decrease in force‐generation capacity. These observations may have important implications for our understanding of the pathophysiological processes of muscle weakness seen in inflammatory myopathies. Muscle Nerve, 2008