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In the wobbler (WR) mouse, an L967Q missense mutation in the vesicular protein\u2010sorting factor VPS54 causes motor neuron degeneration and globozoospermia. Although electron microscopy of WR testis shows all major components of spermatogenesis, they appear in a deranged morphology that prevents the formation of the acrosome. In order to determine proteome\u2010wide changes, affected testes were analysed by 2D\u2010DIGE and MS. The concentration of 8 proteins was increased and that of 35 proteins decreased as compared to wild type. Mass spectrometric analysis identified proteins with an altered concentration to be associated with metabolite transport, fatty acid metabolism, cellular interactions, microtubule assembly and stress response (chaperones Hsp70\u20132 and Hsp90\u03b1). Minor changes were observed for proteins involved in cell redox homeostasis, cytoskeleton formation, PTMs, detoxification and metabolism. The most dramatically decreased protein in WR testis was identified as fatty acid binding protein FABP3, as confirmed by immunoblot analysis. We conclude that a missense mutation in VPS54, an essential component of the Golgi\u2010associated retrograde protein complex, not only prevents the formation of an acrosome but also initiates a cascade of metabolic abnormalities and a stress reaction.<\/jats:p>","DOI":"10.1002\/pmic.201300189","type":"journal-article","created":{"date-parts":[[2013,10,11]],"date-time":"2013-10-11T21:53:02Z","timestamp":1381528382000},"page":"839-852","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Pathoproteomics of testicular tissue deficient in the GARP component VPS54: The wobbler mouse model of globozoospermia"],"prefix":"10.1002","volume":"14","author":[{"given":"Harald","family":"Jockusch","sequence":"first","affiliation":[{"name":"Department of Developmental Biology and Molecular Pathology University of Bielefeld  Bielefeld 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