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In this study, we used two different experimental setups of 2,8\u2010dihydroxyadenine\u2010induced nephropathy in different mouse strains to develop a non\u2010invasive mouse model of uremic cardiomyopathy. Among the different models, only 129\/Sv mice fed an adenine\u2010supplemented diet for 16\u2009weeks showed typical features of uremic cardiomyopathy. Kidney damage was confirmed by histopathologic findings of diffuse fibrosis with collagen deposition, crystal formation, and uremia. The cardiac phenotype showed significantly increased myocardial fibrosis associated with impaired cardiac contractility under dobutamine\u2010induced stress conditions. This was associated with a significant activation of the mTOR pathway and downstream endoplasmic reticulum stress, increased apoptosis, and inflammation. Treatment of 129\/Sv mice with an adenine\u2010supplemented diet for 16\u2009weeks represents a model of uremic cardiomyopathy with increased myocardial fibrosis and impaired cardiac function, as well as a shift from cardioprotective to detrimental signaling, increased endoplasmic reticulum stress, and inflammation.<\/jats:p>","DOI":"10.1096\/fj.202500281r","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T06:59:56Z","timestamp":1747637996000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Development of a Mouse Model of Uremic Cardiomyopathy: Investigating the Impact of Chronic Kidney Disease on Cardiac Function and Signaling Pathway"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8066-6114","authenticated-orcid":false,"given":"Julia","family":"Moellmann","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I 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