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High-Resolution Targeted Quantitation: Biomarker Discovery in a Mouse Transgenic Model of Myopathy

Reputable Mentor II
Reputable Mentor II
Dauly C, Freret M, Drouot L, Ho J, Cosette P, Boyer O.
Application Note 555
Normal muscle fibers do not express detectable levels of class I major histocompatibility complex (MHC-I). In contrast, high-level expression of MHC-I is a hallmark of muscle autoimmune diseases such as polymyositis, inclusion-body myositis or dermatomyositis. It is generally considered that damage of muscle fibers in myositis results from an auto-immune attack by auto-reactive cytotoxic T lymphocytes (CTLs) that recognize muscle autoantigens presented by MHC-I molecules. We used a MHC-I–transgenic mouse model in which a controllable muscle-specific promoter governs the conditional up-regulation of a MHC-I molecule (H-2Kb) in skeletal muscle resulting in severe myopathy. A proteomic study was performed on mouse muscle tissue to evaluate the consequences of this forced H-2Kb expression. An experimental workflow was designed including protein digestion and label-free qualitative and quantitative analysis by high-resolution, accurate mass LC-MS/MS. Three muscle tissues from MHC-I–inducible mice were compared to two healthy controls using a differential analysis and targeted quantitation approach.

Thermo Fisher Scientific
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‎10-15-2021 11:13 AM
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