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    Proteomic identification of elevated saliva kallikrein levels in the mdx-4cv mouse model of Duchenne muscular dystrophy

    Murphy, Sandra and Zweyer, Margit and Mundegar, Rustam R. and Swandulla, Dieter and Ohlendieck, Kay (2018) Proteomic identification of elevated saliva kallikrein levels in the mdx-4cv mouse model of Duchenne muscular dystrophy. Biochemistry and Biophysics Reports, 18 (100541). ISSN 2405-5808

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    Dystrophinopathies are multi-system disorders that affect the skeletal musculature, the cardio-respiratory system and the central nervous system. The systematic screening of suitable biofluids for released or altered proteins promises new insights into the highly complex pathophysiology of X-linked muscular dystrophy. However, standard detection approaches using antibody-based assays often fail to reproducibly detect low-abundance protein isoforms in dilute biological fluids. In contrast, mass spectrometric screening approaches enable the proteome-wide identification of minor protein changes in biofluids. This report describes the findings from the comparative proteomic analysis of whole saliva samples from wild type versus the established mdx-4cv mouse model of highly progressive muscular dystrophy, focusing on the kallikrein protein family. Kallikrein-1 (Klk1) and 13 Klk1-related peptidases were identified in saliva and serum from normal mice. Comparative proteomics revealed elevated saliva levels of the Klk1-related peptidases Klk1-b1, Klk1-b5 and Klk-b22, as well as an increased Klk-1 concentration, which agrees with higher Klk-1 levels in serum from mdx-4cv mice. This indicates altered cellular signaling, extracellular matrix remodeling and an altered immune response in the mdx-4cv mouse, and establishes liquid biopsy procedures as suitable bioanalytical tools for the systematic survey of complex pathobiochemical changes in animal models of muscular dystrophy.

    Item Type: Article
    Keywords: Dystrophinopathy; Kallikrein-1; Kallikrein-related peptidase; Klk; Saliva proteomics; X-linked muscular dystrophy;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 13139
    Identification Number:
    Depositing User: Prof. Kay Ohlendieck
    Date Deposited: 22 Jul 2020 15:24
    Journal or Publication Title: Biochemistry and Biophysics Reports
    Publisher: Elsevier
    Refereed: Yes
    Funders: Hume scholarship (Maynooth University), Muscular Dystrophy Ireland, Health Research Board (HRB), Science Foundation Ireland (SFI)
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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