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Heterozygous <jats:italic>TTN<\/jats:italic> truncating variants (TTNtv) increase the risk of a cardiomyopathy. At the same time, TTNtv and few missense variants have been identified in patients with mainly recessive skeletal muscle diseases. The pathogenic mechanisms underlying titin\u2010related diseases are still partly unknown. Similarly, the titin mechanical and functional role in the muscle contraction are far from being exhaustively clarified. In the last few years, several animal models carrying variants in the titin gene have been developed and characterized to study the structural and mechanical properties of specific titin domains or to mimic patients' mutations. This review describes the main animal models so far characterized, including eight mice models and three fish models (Medaka and Zebrafish) and discusses the useful insights provided by a thorough characterization of the cell\u2010, tissue\u2010 and organism\u2010phenotypes in these models.<\/jats:p>","DOI":"10.1111\/jcmm.17533","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T10:11:15Z","timestamp":1662459075000},"page":"5103-5112","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Use of animal models to understand titin physiology and pathology"],"prefix":"10.1111","volume":"26","author":[{"given":"Matteo","family":"Marcello","sequence":"first","affiliation":[{"name":"PhysioLab Universit\u00e0 di Firenze  Sesto Fiorentino 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