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Use of animal models to understand titin physiology and pathology
Matteo Marcello1, Viviana Cetrangolo1, Marco Savarese2,3
1PhysioLab, Università di Firenze, Sesto Fiorentino, Italy.
Abstract:
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.
Insights
Titin (TTN) mutations are linked to heart and skeletal muscle diseases. This review details TTN animal models, offering insights into titin
Area of Science:
- Molecular Biology
- Genetics
- Biophysics
Background:
- Titin (TTN) mutations are increasingly recognized as a cause of both cardiomyopathy and skeletal muscle diseases.
- The precise mechanisms driving titin-related disorders and titin's exact role in muscle contraction remain incompletely understood.
- Existing research highlights the significance of titin truncating variants (TTNtv) and missense variants in disease pathogenesis.
Purpose of the Study:
- To review and describe characterized animal models of titin gene variants.
- To discuss the insights gained from these models regarding titin's function and disease mechanisms.
- To provide a comprehensive overview of available TTN research models for the scientific community.
Main Methods:
- Systematic review of literature on animal models for titin gene mutations.
- Characterization of eight mouse models and three fish models (Medaka and Zebrafish) carrying TTN variants.
- Analysis of cell-, tissue-, and organism-level phenotypes in these models.
Main Results:
- Identified and described eight mouse models and three fish models (Medaka, Zebrafish) with titin gene variants.
- These models exhibit diverse phenotypes relevant to titin-related cardiomyopathies and skeletal muscle disorders.
- Detailed characterization of these models provides valuable data on titin's structural and mechanical properties.
Conclusions:
- Animal models are crucial for investigating the complex roles of titin in muscle function and disease.
- The reviewed models offer powerful tools to elucidate pathogenic mechanisms of titin-related diseases.
- Further research using these models will advance our understanding of titin's mechanical and functional significance.
