Key result
Titin variant animal models clarify structural properties and pathogenic mechanisms of titin-related cardiomyopathy.
Why the study?
Pathogenic mechanisms underlying titin-related diseases and titin's mechanical and functional role in muscle contraction remain incompletely understood.
Animal models of titin mutations provide crucial insights into the pathogenic mechanisms underlying titin-related cardiomyopathies and skeletal muscle diseases.
In recent years, increasing attention has been paid to titin (TTN) and its mutations. Heterozygous TTN 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-related 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-, tissue- and organism-phenotypes in these models.
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Marcello et al. (2022) conducted a review in Titinopathies. Animal models of titin mutations was evaluated. Animal models carrying variants in the titin gene provide critical insights into titin structural properties and the pathogenic mechanisms underlying titin-related cardiomyopathies and myopathies.
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