{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:30:47Z","timestamp":1791462647840,"version":"4.3.4"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,9,14]],"date-time":"2025-09-14T00:00:00Z","timestamp":1757808000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,14]],"date-time":"2025-09-14T00:00:00Z","timestamp":1757808000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100010275","name":"Deutsche Gesellschaft f\u00fcr Muskelkranke","doi-asserted-by":"publisher","award":["Cl3\/2"],"award-info":[{"award-number":["Cl3\/2"]}],"id":[{"id":"10.13039\/501100010275","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The classical morphological hallmarks of the clinically and genetically diverse group of human myofibrillar myopathies are signs of myofibrillar degeneration and desmin\u2010positive protein aggregates. The local sarcomeric enrichment of filamin\u2010C and xin actin\u2010binding repeat\u2010containing proteins 1 and 2 (xirp 1 and xirp 2) is a marker of myofibrillar damage. This work aimed to (i) address filamin\u2010C\u2010 and xirp 1\/2\u2010positive sarcomeric lesions in desminopathy mouse models, (ii) develop an approach to quantifying xirp 1\/2\u2010positive sarcomeric lesions, and (iii) study the effects of acute physical exercise on sarcomeric lesion formation in R349P desmin knock\u2010in mice, which are a model of human R350P desminopathy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sarcomeric lesions were visualised by xirp 1\/2 and filamin\u2010C immunofluorescence in soleus muscles from R349P and R405W desmin knock\u2010in, desmin knock\u2010out and W2711X filamin\u2010C knock\u2010in mice. The open\u2010source software QuPath was used to analyse xirp 1\/2 confocal immunofluorescence images of soleus muscle from nonexercised and treadmill\u2010exercised R349P desmin knock\u2010in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Filamin\u2010C and xirp 1\/2 stained muscles revealed the presence of congenerous sarcomeric lesions in heterozygous and homozygous R349P and R405W desmin knock\u2010in, homozygous desmin knock\u2010out and heterozygous and homozygous W2711X filamin\u2010C knock\u2010in mice. Quantitative analysis of R349P desmin knock\u2010in mice showed (i) significantly more lesions in nonexercised heterozygous mice, with an even more pronounced increase in homozygous animals, as compared to wild\u2010type, and (ii) a significant increase in sarcomeric lesions per mm\n                      <jats:sup>2<\/jats:sup>\n                      in heterozygous mice and wild\u2010type siblings subjected to strenuous treadmilling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A QuPath workflow to quantify sarcomeric lesions using xirp 1\/2 immunofluorescence images showed augmented densities of lesions in R349P desminopathy mice and after treadmill exercise. Eccentric and high\u2010intensity physical activity may exhibit a disease\u2010promoting effect on skeletal muscles in desminopathy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.70038","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T01:29:28Z","timestamp":1757899768000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Quantification of Exercise\u2010Induced Sarcomeric Damage in R349P Desmin Knock\u2010In Mice: A New Approach in Myofibrillar Myopathy Research"],"prefix":"10.1111","volume":"51","author":[{"given":"Christian","family":"Holtzhausen","sequence":"first","affiliation":[{"name":"Institute of Neuropathology Universit\u00e4tsklinikum Erlangen, Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg (FAU)  Erlangen 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