Open AccessUse of animal models to understand titin physiology and pathology
Author(s) -
Marcello Matteo,
Cetrangolo Viviana,
Savarese Marco,
Udd Bjarne
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17533
Subject(s) - titin , obscurin , zebrafish , phenotype , missense mutation , biology , cardiomyopathy , model organism , genetics , gene , sarcomere , computational biology , pathology , bioinformatics , myocyte , medicine , microbiology and biotechnology , heart failure
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.