The Effects And Mechanism Of Action Of Gata4 H435Y Mutation On Cardiac Function In Mice

Objective To investigate the impact of Gata4 gene H435 Y mutation on heart function with the changes of cardiac tissue mRNA and protein expressions in mice.Methods The group has successfully constructed the G4354 H435 Y site mutation mouse model in the early stage.Our research included in 2 groups: Wildtype(WT)mice group and Gata4 H435 Y mutant(Gata4 H435Y)mice group,6 mice in each group.Each mouse was 8 weeks old.Examining and comparing the heart function and the ratio of heart weight to body weight(HW/BW)between 2 groups;cardiac tissue morphology was observed by Masson staining;mRNA and protein expressions of Gata4,Sox9,Scleraxis,Tenascin and Aggrecan were determined by RT-PCR and Western blot analysis.Results Compared with the WT group,the left ventricular ejection fraction(LVEF)and left ventricular systolic fraction(LVFS)were decreased(P<0.05),and the left ventricular end-systolic diameter(LVIDs)was increased in the Gata4 H435 Y group(P<0.05),the difference was statistically significant.The left ventricular end-diastolic diameter(LVIDd)of Gata4 H435 Y group was slightly increased compared with WT group,but it was not statistically significant(p>0.05).There was no significant difference in the gross visual observation between the two groups of mice.The weight of the Gata4 H435 Y group was lower than that of the WT group,but the difference was not statistically significant.The Gata4 H435 Y group had weight loss,heart weight/weight compared with the WT group.The difference was statistically significant(P<0.05).Masson staining showed no significant difference in myocardial fiber between the two groups.However,compared with the WT group,the Gata4 H435 Y group had milder myocardial collagen fiber staining and significantly reduced staining area(P<0.05).Compared with the WT group,the expression of Gata4,Scleraxis and Sox9 genes and protein in the Gata4 H435 Y group was significantly decreased(P<0.05).Aggrecan and Tenascin decreased,but the difference was not statistically significant(p>0.05).Conclusion Gata4 gene H435 Y mutation may impair the heart function in experimental mice by reducing Gata4 and downstream gene expression,which may lead to the decrease of myocardial collagen fiber content,affecting mouse heart development and impairing the heart function of mice.