Work

Mutations in Filamin C Associated with Both Alleles Do Not Affect the Functioning of Mice Cardiac Muscles

Year: 2025

Type: article

Abstract: 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.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms26041409