Blog
About

  • Record: found
  • Abstract: found
  • Article: found
Is Open Access

Applications of metabolomics and proteomics to the mdx mouse model of Duchenne muscular dystrophy: lessons from downstream of the transcriptome

, 1 , 2

Genome Medicine

BioMed Central

Read this article at

Bookmark
      There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

      Abstract

      Functional genomic studies are dominated by transcriptomic approaches, in part reflecting the vast amount of information that can be obtained, the ability to amplify mRNA and the availability of commercially standardized functional genomic DNA microarrays and related techniques. This can be contrasted with proteomics, metabolomics and metabolic flux analysis (fluxomics), which have all been much slower in development, despite these techniques each providing a unique viewpoint of what is happening in the overall biological system. Here, we give an overview of developments in these fields 'downstream' of the transcriptome by considering the characterization of one particular, but widely used, mouse model of human disease. The mdx mouse is a model of Duchenne muscular dystrophy (DMD) and has been widely used to understand the progressive skeletal muscle wasting that accompanies DMD, and more recently the associated cardiomyopathy, as well as to unravel the roles of the other isoforms of dystrophin, such as those found in the brain. Studies using proteomics, metabolomics and fluxomics have characterized perturbations in calcium homeostasis in dystrophic skeletal muscle, provided an understanding of the role of dystrophin in skeletal muscle regeneration, and defined the changes in substrate energy metabolism in the working heart. More importantly, they all point to perturbations in proteins, metabolites and metabolic fluxes reflecting mitochondrial energetic alterations, even in the early stage of the dystrophic pathology. Philosophically, these studies also illustrate an important lesson relevant to both functional genomics and the mouse phenotyping in that the knowledge generated has advanced our understanding of cell biology and physiological organization as much as it has advanced our understanding of the disease.

      Related collections

      Most cited references 92

      • Record: found
      • Abstract: found
      • Article: not found

      Initial sequencing and analysis of the human genome.

       James Galagan (2001)
      The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.
        Bookmark
        • Record: found
        • Abstract: found
        • Article: not found

        Initial sequencing and comparative analysis of the mouse genome.

        The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism.
          Bookmark
          • Record: found
          • Abstract: found
          • Article: not found

          Dystrophin: the protein product of the Duchenne muscular dystrophy locus.

          The protein product of the human Duchenne muscular dystrophy locus (DMD) and its mouse homolog (mDMD) have been identified by using polyclonal antibodies directed against fusion proteins containing two distinct regions of the mDMD cDNA. The DMD protein is shown to be approximately 400 kd and to represent approximately 0.002% of total striated muscle protein. This protein is also detected in smooth muscle (stomach). Muscle tissue isolated from both DMD-affected boys and mdx mice contained no detectable DMD protein, suggesting that these genetic disorders are homologous. Since mdx mice present no obvious clinical abnormalities, the identification of the mdx mouse as an animal model for DMD has important implications with regard to the etiology of the lethal DMD phenotype. We have named the protein dystrophin because of its identification via the isolation of the Duchenne muscular dystrophy locus.
            Bookmark

            Author and article information

            Affiliations
            [1 ]Department of Biochemistry, Tennis Court Road, University of Cambridge, Cambridge, CB2 1QW, UK
            [2 ]Department of Nutrition and Montreal Heart Institute, Université de Montréal, Montreal, Quebec H3C 3J7, Canada
            Contributors
            Journal
            Genome Med
            Genome Medicine
            BioMed Central
            1756-994X
            2009
            25 March 2009
            : 1
            : 3
            : 32
            2664943
            gm32
            19341503
            10.1186/gm32
            Copyright ©2009 BioMed Central Ltd
            Categories
            Review

            Molecular medicine

            Comments

            Comment on this article