Fig. 1: Outflow tract defects in heart-specific Smc3-knockout mice.

a Location of Smc3 expression in mouse heart at embryonic day (E) 10.5 (top panel) and postnatal day (P) 0 (bottom panel). RNA fluorescence in situ hybridization was performed using the RNA scope platform with probes targeting Smc3. Image scale bars, 0.2 mm. b Temporal expression pattern of Smc3 in mouse hearts from E9.5 to P7 determined using quantitative real-time PCR (qPCR). c Genotype distribution of embryos and newborn mice resulting from Smc3^fl/fl and Smc3^fl/+; Nkx2.5-Cre crosses. d Representative necropsy images of the ventricular size, length of the outflow tract (OFT), and relative location of the aorta (AO) and pulmonary artery (PA) in Smc3^fl/fl, Smc3^fl/+; Nkx2.5-Cre, and Smc3^fl/fl; Nkx2.5-Cre embryos at E9.5, E10.5, E11.5, E12.5, and E13.5. Image scale bars, 1 mm. e Representative images of hearts from fetal and newborn Smc3^fl/fl and Smc3^fl/+; Nkx2.5-Cre mice at E14.5, E18.5, and P0. Compared with Smc3^fl/fl hearts, Smc3^fl/+; Nkx2.5-Cre hearts have different degrees of abnormal arrangement of the large arteries. Image scale bars, 2 mm. f H&E staining of heart sections from Smc3^fl/fl and Smc3^fl/+; Nkx2.5-Cre mice at E14.5 and P0. A ventricular septal defect (VSD) was observed in 6/18 Smc3^fl/+; Nkx2.5-Cre mice at E14.5. In 2/18 Smc3^fl/+; Nkx2.5-Cre mice at E14.5, the PA connects to the left ventricle (LV), and the AO connects to the right ventricle (RV). Scale bars for images of E14.5 embryos, 0.5 mm; scale bars for images of P0 mice, 0.25 mm. g H&E staining of heart sections from Smc3^fl/fl and Smc3^fl/+; Nkx2.5-Cre mice at E18.5 (left panel) and quantification of the RV wall compact zone thickness at E14.5 and E18.5 (right panel). The compact layer of the ventricular myocardium is indicated by the black line. Image scale bars, 0.25 mm. The error bars indicate the means ± standard deviations. *P < 0.05 and **P < 0.01. TGA transposition of the great arteries, RA right atrium, LA left atrium.