Figure 7. Gata4 G295S mutation has in vivo functional deficits in the early embryonic myocardium.

(A) Embryonic lethality by E10.5 was found in compound heterozygote mice expressing only a Gata4 G295S mutant allele in early myocardium with the Nkx2-5-Cre, but normal Mendelian ratios were seen when the Gata4 G295S mutant allele was expressed in endocardium and late myocardium using Tie2-Cre and α-MHC-Cre, respectively. Images (B, D, F, H, J, L) and histologic sections (C, E, G, I, K, M) of E10.5 embryos generated with Tie2-Cre, which is specific for endocardium (B–E); α-MHC-Cre, which is specific for late embryonic myocardium (F–I); and Nkx2.5-Cre, which is specific for early embryonic myocardium (J–M), are shown. (L,M) Growth retardation and myocardial thinning were seen in Gata4 G295S^ki/flox; Nkx2-5-Cre⁺ E10.5 embryos similar to the phenotype of the Gata4 G295S^ki/ki embryo. (H,I) The hearts of Gata4 G295S^ki/flox; α-MHC-Cre⁺ appeared normal at E10.5. (D,E) While the Gata4 G295S^ki/flox; Tie2-Cre⁺ did not show growth retardation or myocardial thinning, hypocellular endocardial cushions were noted (*). A, atria; V, ventricle; scale bars indicate 200 µm.