The actin-organizing formin protein Fhod3 is required for postnatal development and functional maintenance of the adult heart in mice

• DOI: 10.1074/jbc.m117.813931
• Publication Date: 2017-11-20T21:50:14Z
• Authors: Tomoki Ushijima; Noriko Fujimoto; Sho Matsuyama; Meikun Kan-o; Hiroshi Kiyonari; Go Shioi; Yohko Kage; Sho Yamasaki; Ryu Takeya; Hideki Sumimoto
• Keywords: Heart development; Formins

Cardiac development and function require actin–myosin interactions in the sarcomere, a highly organized contractile structure. Sarcomere assembly mediated by formin homology 2 domain-containing 3 (Fhod3), member of formins that directs formation straight actin filaments, is essential for embryonic cardiogenesis. However, role Fhod3 neonatal adult stages has remained unknown. Here, we generated floxed mice to bypass lethality an knockout (KO). Perinatal KO heart caused juvenile at around day 10 after birth with enlarged hearts composed severely impaired myofibrils, indicating crucial postnatal development. Tamoxifen-induced conditional neither led lethal effects nor did it affect sarcomere structure localization components. Fhod3-deleted exhibited slight cardiomegaly mild impairment cardiac function, conditions were sustained over 1 year without compensation during aging. In addition these age-related changes, systemic stimulation α1-adrenergic receptor agonist phenylephrine, which induces hypertension hypertrophy development, induced expression fetal genes was more pronounced than control mice, suggesting modulates hypertrophic changes heart. We conclude plays both functional maintenance