This review critically examines the evolving landscape of genetic animal models for investigating cardiovascular diseases (CVDs). We analyze established models, including spontaneously hypertensive rats, Watanabe hyperlipidemic rabbits, etc., and transgenic models that have advanced our understanding of essential and secondary hypertension, atherosclerosis, and non-ischemic diseases of the heart. This review systematically evaluates the translational strengths and physiological limitations of these approaches across species barriers. Particular attention is paid to emerging technologies—AAV-mediated gene delivery, CRISPR-Cas9 editing, and chemogenetic tools—that enable unprecedented precision in manipulating cardiac-specific gene expression to study pathophysiological mechanisms. We address persistent challenges including off-target effects and transgene expression variability, while highlighting innovations in synthetic vectors and tissue-specific targeting strategies. This synthesis underscores how evolving genetic technologies are revolutionizing cardiovascular research paradigms, offering refined disease models and optimized therapeutic interventions that pave the way toward personalized medicine approaches for the world’s leading cause of mortality.

Filamin C (FLNC) is a structural protein of muscle fibers. Mutations in the FLNC gene are known to cause myopathies and cardiomyopathies in humans. Here we report the generation by a CRISPR/Cas9 editing system injected into zygote pronuclei of two mouse strains carrying filamin C mutations—one of them (AGA) has a deletion of three nucleotides at position c.7418_7420, causing E>>D substitution and N deletion at positions 2472 and 2473, respectively. The other strain carries a deletion of GA nucleotides at position c.7419_7420, leading to a frameshift and a premature stop codon. Homozygous animals (Flnc^AGA/AGA and Flnc^GA/GA) were embryonically lethal. We determined that Flnc^GA/GA embryos died prior to the E12.5 stage and illustrated delayed development after the E9.5 stage. We performed histological analysis of heart tissue and skeletal muscles of heterozygous strains carrying mutations in different combinations (Flnc^GA/wt, Flnc^AGA/wt, and Flnc^GA/AGA). By performing physiological tests (grip strength and endurance tests), we have shown that heterozygous animals of both strains (Flnc^GA/wt, Flnc^AGA/wt) are functionally indistinguishable from wild-type animals. Interestingly, compound heterozygous mice (Flnc^GA/AGA) are viable, develop normally, reach puberty and it was verified by ECG and Eco-CG that their cardiac muscle is functionally normal. Intriguingly, Flnc^GA/AGA mice demonstrated better results in the grip strength physiological test in comparison to WT animals. We also propose a structural model that explains the complementary interaction of two mutant variants of filamin C.

Filamin C (FLNC) is a structural protein of muscle fibers. Mutations in the Flnc gene are known to cause myopathies and cardiomyopathies in humans. Here we report a generation of two mouse strains carrying filamin C mutations — one of them has a deletion of three nucleotides at position c.7418_7420, causing E>>;D substitution and N deletion at positions 2472 and 2473, respectively. The other strain carries a deletion of GA nucleotides at position c.7419_7420, leading to a frameshift and a premature stop-codon. We have shown that heterozygous animals of both strains are functionally and morphologically indistinguishable from wild type animals, while homozygosity is embryonically lethal. Interestingly, compound heterozygous mice are viable, develop normally, reach puberty and their cardiac muscle is functionally and histologically normal. We also propose a structural model that explains the complementary interaction of two mutant variants of filamin C.