Overexpression of MHC class I heavy chain protein in young skeletal muscle leads to severe myositis: implications for juvenile myositis

Li, Charles Kwok-chong, Knopp, Paul, Moncrieffe, Halima, Singh, Bhanu, Shah, Sonia, Nagaraju, Kanneboyina, Varsani, Hemlata, Gao, Bin and Wedderburn, Lucy R. (2009) Overexpression of MHC class I heavy chain protein in young skeletal muscle leads to severe myositis: implications for juvenile myositis. American Journal of Pathology, 175 3: 1030-1040. doi:10.2353/ajpath.2009.090196


Author Li, Charles Kwok-chong
Knopp, Paul
Moncrieffe, Halima
Singh, Bhanu
Shah, Sonia
Nagaraju, Kanneboyina
Varsani, Hemlata
Gao, Bin
Wedderburn, Lucy R.
Title Overexpression of MHC class I heavy chain protein in young skeletal muscle leads to severe myositis: implications for juvenile myositis
Journal name American Journal of Pathology   Check publisher's open access policy
ISSN 0002-9440
1525-2191
Publication date 2009
Sub-type Article (original research)
DOI 10.2353/ajpath.2009.090196
Open Access Status
Volume 175
Issue 3
Start page 1030
End page 1040
Total pages 11
Place of publication New York, NY, United States
Publisher Elsevier
Language eng
Abstract Folding and transport of proteins, such as major histocompatibility complex (MHC) class I , through the endoplasmic reticulum (ER) is tightly regulated in all cells, including muscle tissue, where the specialized ER sarcoplasmic reticulum is also critical to muscle fiber function. Overexpression of MHC class I protein is a common feature of many muscle pathologies including idiopathic myositis and can induce ER stress. However, there has been no comparison of the consequences of MHC overexpression in muscle at different ages. We have adapted a transgenic model of myositis induced by overexpression of MHC class I protein in skeletal muscle to investigate the effects of this protein overload on young muscle fibers, as compared with adult tissue. We find a markedly more severe disease phenotype in young mice, with rapid onset of muscle weakness and pathology. Gene expression profiling to compare the two models indicates rapid onset of ER stress in young muscle tissue but also that gene expression of key muscle structural proteins is affected more rapidly in young mice than adults after this insult. This novel model has important implications for our understanding of muscle pathology in dermatomyositis of both adults and children. Copyright
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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