biostudies-literatureHoltzhausen CDeutsche Forschungsgemeinschaft (DFG)Deutsche Gesellschaft für MuskelkrankeDeutsche Gesellschaft für Muskelkranke (DGM)Interdisciplinary Center for Clinical Research (IZKF), Universitätsklinikum Erlangene70038https://www.ebi.ac.uk/biostudies/studies/S-EPMC12433831biostudies-literatureUnknown51(5)<h4>Aims</h4>The classical morphological hallmarks of the clinically and genetically diverse group of human myofibrillar myopathies are signs of myofibrillar degeneration and desmin-positive protein aggregates. The local sarcomeric enrichment of filamin-C and xin actin-binding repeat-containing proteins 1 and 2 (xirp 1 and xirp 2) is a marker of myofibrillar damage. This work aimed to (i) address filamin-C- and xirp 1/2-positive sarcomeric lesions in desminopathy mouse models, (ii) develop an approach to quantifying xirp 1/2-positive sarcomeric lesions, and (iii) study the effects of acute physical exercise on sarcomeric lesion formation in R349P desmin knock-in mice, which are a model of human R350P desminopathy.<h4>Methods</h4>Sarcomeric lesions were visualised by xirp 1/2 and filamin-C Neuropathology and applied neurobiologyQuantification of Exercise-Induced Sarcomeric Damage in R349P Desmin Knock-In Mice: A New Approach in Myofibrillar Myopathy Research.PMC12433831CL 381/12-1SCHR 562/22-1FU 339/13-1SCHR 562/19-1Cl3/2Schultheis Dvan der Ven PFMSchlotzer-Schrehardt URiehl-Nestler MBerwanger CMahabir EClemen CSHoltzhausen CBatonnet-Pichon SSchroder RSchuld JFurst DOLilienbaum AfalseQuantification of Exercise-Induced Sarcomeric Damage in R349P Desmin Knock-In Mice: A New Approach in Myofibrillar Myopathy Research.<h4>Aims</h4>The classical morphological hallmarks of the clinically and genetically diverse group of human myofibrillar myopathies are signs of myofibrillar degeneration and desmin-positive protein aggregates. The local sarcomeric enrichment of filamin-C and xin actin-binding repeat-containing proteins 1 and 2 (xirp 1 and xirp 2) is a marker of myofibrillar damage. This work aimed to (i) address filamin-C- and xirp 1/2-positive sarcomeric lesions in desminopathy mouse models, (ii) develop an approach to quantifying xirp 1/2-positive sarcomeric lesions, and (iii) study the effects of acute physical exercise on sarcomeric lesion formation in R349P desmin knock-in mice, which are a model of human R350P desminopathy.<h4>Methods</h4>Sarcomeric lesions were visualised by xirp 1/2 and filamin-C 2025-01-01T00:00:00Z2025 Oct2026-06-01T14:02:12.539Z2026-04-08T13:10:24.745ZS-EPMC124338314094730910.1111/nan.70038