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Mutation-independent Proteomic Signatures of Pathological Progression in Murine Models of Duchenne Muscular Dystrophy
Authors:Tirsa L E van Westering  Henrik J Johansson  Britt Hanson  Anna M L Coenen-Stass  Yulia Lomonosova  Jun Tanihata  Norio Motohashi  Toshifumi Yokota  Shin'ichi Takeda  Janne Lehti  Matthew J A Wood  Samir EL Andaloussi  Yoshitsugu Aoki  Thomas C Roberts
Institution:1. Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK;2. Department of Oncology/Pathology, Cancer Proteomics Mass Spectrometry, SciLifeLab Stockholm, Karolinska Institutet, Stockholm, Sweden;3. Department of Paediatrics, University of Oxford, Oxford, UK;4. Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo, Japan;5. Department of Medical, Genetics, School of Human Development Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada;6. MDUK Oxford Neuromuscular Centre, Oxford, UK;7. Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden
Abstract:
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  • Highlights
    • ?Proteomics analysis was performed in two murine models of Duchenne muscular dystrophy (mdx and mdx52) at three ages (8, 16 and 80 weeks) and compared with wild-type controls.
    • ?High-resolution isoelectric focusing liquid chromatography-tandem mass spectrometry enabled the quantification of 4974 proteins in all samples.
    • ?This study has revealed protein signatures of dystrophin deficiency and the progression of dystrophic pathology.
    • ?In contrast, the proteomes of the mdx and mdx52 mice were highly similar.
    • ?Pathway analysis revealed crosstalk between inflammatory, metabolic and muscle growth processes in dystrophic muscle.
    Keywords:tandem mass spectrometry  iTRAQ  neurodegenerative diseases  quantification  gene expression  Duchenne muscular dystrophy  dystrophin  mdx  mdx52  proteomics
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