GATA4 transgenic mice as an in vivo model of congenital heart disease

Our previous study indicated that 8 patients from a family with a history of congenital heart disease had simple atrial septal defect (ASD) and carried the same mutation at codon 310 in the GATA4 gene. In the present study, to identify the functional defects caused by this mutation in an in vivo model, the transgene DNA constructs were microinjected into mice to generate a transgenic mouse model. The mice were genotyped using PCR and DNA sequencing. Protein expression was measured by western blot analysis. qPCR was used to determine the copy number of the transgenes. The heart tissue was fixed and sectioned by conventional procedures. The Vevo 2000 system was used to perform echocardiography on the mice. The expression of GATA4 target genes was measured using the real-time PCR system. The incidence of ASD in the heterozygous transgenic mice was found to be greater than that in the wild-type control mice (P<0.05). In addition, the expression of α-myosin heavy chain (α-MHC) in the heart tissues from the homozygous mice was lower than that in the heart tissues from their wild-type littermates (P<0.05). In conclusion, these results suggest that the introduction of GATA4 M310V negatively affects the normal expression of α-MHC. In accordance with previous findings on GATA4 mutation screening and in vitro experiments, this study confirms that GATA4 M310V mutation may lead to the development of the congenital heart defect, ASD.