title: Myocardial deletion of Smad4 using a novel α skeletal muscle actin Cre recombinase transgenic mouse causes misalignment of the cardiac outflow tract.
abstract: SMAD4 acts as the converging point for TGFβ and BMP signaling in heart development. Here, we investigated the role of SMAD4 in heart development using a novel α skeletal muscle actin Cre recombinase (MuCre) transgenic mouse strain. Lineage tracing using MuCre/ROSA26(LacZ) reporter mice indicated strong Cre-recombinase expression in developing and adult heart and skeletal muscles. In heart development, significant MuCre expression was noted at E11.5 in the atrial, ventricular, outflow tract and atrioventricular canal myocardium, but not in the endocardial cushions. MuCre-driven conditional deletion of Smad4 in mice caused double outlet right ventricle (DORV), ventricular septal defect (VSD), impaired trabeculation and thinning of ventricular myocardium, and mid-gestational embryonic lethality. In conclusion, MuCre mice effectively delete genes in both heart and skeletal muscles, thus enabling the discovery that myocardial Smad4 deletion causes misalignment of the outflow tract and DORV.
authors.affiliation: BIO5 Institute, and Department of Cell Biology and Anatomy, University of Arizona, Tucson, AZ 85724, USA. azharm@email.arizona.edu
authors.forename: Mohamad
authors.initials: M
authors.lastname: Azhar
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Wang
authors.forename: Tony
authors.initials: T
authors.lastname: Frugier
authors.forename: Kyoko
authors.initials: K
authors.lastname: Koishi
authors.forename: Chuxia
authors.initials: C
authors.lastname: Deng
authors.forename: Peter G
authors.initials: PG
authors.lastname: Noakes
authors.forename: Ian S
authors.initials: IS
authors.lastname: McLennan
mesh_terms: D000818:Animals; D006321:Heart / Q000196:embryology*; D006801:Humans; D019426:Integrases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D051901:Smad4 Protein; C045073:Cre recombinase; D019426:Integrases