Actn2F/F mice have loxP site flanking exons 2-4 of the actinin alpha 2 (Actn2) gene. Actn2 encodes a muscle-specific, alpha actinin isoform that is expressed in both skeletal and cardiac muscles where it anchors the myofibrillar actin filaments. Mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, or treated with an Adeno-associated viral (AAV)-Cre, resulting offspring will have exons 2-4 removed in the Cre-expressing tissues of the offspring. The predominant transcript after Cre recombination is not the expected exon 2-4 deleted transcript but rather a transcript, named Actn2&Delta;E2-6, that results from ectopic splicing of exon 1 to exon 7. These Actn2&Delta;E2-6 mice lack of amino acids 42 to 204, which contain the majority of the actin-binding domains of ACTN2. AAV-mediated expression of Actn2&Delta;E2-6 does not detectably alter cardiomyocyte morphological maturation or overall heart function. Thus, the resulting Actn2&Delta;E2-6 is a hypomorphic mutant that does not exert a dominant-negative impact on cardiomyocyte maturation. This hypomorph is expressed at low levels in the mutant cardiomyocytes as compared to wild-type ACTN2 in control cardiomyocytes. The low level of the mutant ACTN2&Delta;E2-6 protein makes a dominant-negative effect unlikely. Thus, defects in Actn2 mutant cells should be interpreted as the consequence of effective ACTN2 depletion rather than the loss of just the actin-binding domain. Treatment of P1 Actn2F/F pups with AAV9-Tnnt2-Cre, which catalyzes cardiomyocyte selective loxP recombination, results in death 1 week post-injection of a high-dose (3.6 x 109 vg/g) and mid-dose (1.1 x 109 vg/g) due to acute dilated cardiomyopathy, characterized by diminished left ventricular systolic function and dilatation. This coincided with an up-regulation of cardiac stress markers Nppa and Nppb in the groups with cardiac dysfunction. The donating investigator used a low-dose of AAV-Cre (3.6 x 108 vg/g), along with a Cre-inducible fluorescent reporter, to mark ACTN2 expressing cardiomyocytes. This dose recombines 11% of Actn2F/F cardiomyocytes without the heart disfunction associated with the higher dose.

Actn2F/F mice have loxP sites flanking exons 2-4 of the Actn2 gene. This mutant mouse strain may be useful when studying the cell-autonomous roles of sarcomeres in postnatal cardiomyocyte maturation.