Generation of cardiomyocyte-specific ANKRD1 overexpression zebrafish models to investigate pathogenic variants in cardiomyopathy
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Belgrade : Institute of Molecular Genetics and Genetic Engineering
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The ankyrin repeat domain 1 protein (ANKRD1), also known as cardiac ankyrin repeat protein, is a highly conserved multifunctional protein implicated in cardiogenesis, mechanosensing, gene regulation, intracellular signaling, and cardiac stress response. ANKRD1 is predominantly expressed in cardiomyocytes, where it localizes to the nucleus and the sarcomeric I-band. It has been associated with several human cardiac diseases, including dilated, ischemic, and arrhythmogenic cardiomyopathies, as well as end-stage heart failure of various causes. Variants of the ANKRD1 gene, including NM_014391.3(ANKRD1):c.154C>G (p.Pro52Ala) and NM_014391.3(ANKRD1):c.197G>A (p.Arg66Gln), have been linked to congenital atrial septal defects and hypertrophic and dilated cardiomyopathies, but their underlying pathological mechanisms remain unknown. To address this knowledge gap, we are generating three cardiomyocyte-specific ANKRD1 overexpression zebrafish models using the Tol2 transgenesis system. The expression of human wild-type and mutant proteins is driven by the heat-inducible hsp70l promoter and additionally controlled via Cre-mediated recombination. These transgenic lines will be used to longitudinally assess the effects of overexpressing wild-type ANKRD1 as well as the Arg66Gln and Pro52Ala mutations on cardiac development and function. These in vivo models will provide deeper functional insights into ANKRD1’s role in cardiac pathophysiology, facilitating its potential use as a diagnostic, prognostic, or therapeutic target.
BeCELS 2025: Belgrade Conference for Early-Career Life Scientists, taking place on Friday, September 5, 2025, at the Institute of Molecular Genetics and Genetic Engineering (IMGGE) in Belgrade
BeCELS 2025: Belgrade Conference for Early-Career Life Scientists, taking place on Friday, September 5, 2025, at the Institute of Molecular Genetics and Genetic Engineering (IMGGE) in Belgrade