| Congenital heart disease (CHD) is a kind of disease that cause serious damage to human health, the incidence in the newborns is4.05-12.3‰. Environmental factors and genetic factors are the main reasons for congenital heart disease. Among them, intrauterine virus infection is one of the major environmental factors. Clinical epidemiology studies shows that there are at least15virus that may cause abnormal heart development in mice and leading to the occurrence of congenital heart disease. Recently, the study on genetic mechanism of congenital heart disease got a lot of progress. However, the molecular mechanisms of congenital heart disease caused by virus infection remains unclear.In this study, BALB/c mice were used as experimental animals. In order to obtaine H1N1influenza virus infection mice, E7.5d pregnant mice were infected with H1N1influenza virus by nasal dropping according to the development of heart in embryonic. Epigenetic related genes differentially expressed in H1N1influenza virus infection mice which were selected from the genome expression profiling. We focused on BAF chromatin remodeling complex and and its signal pathway, analyzed the gene expression changes of BAF chromatin remodeling related genes, their downstream Wnt signaling and heart development key genes at the RNA and protein levels. We got following research results in this study:1. The epigenetic related gene expression profile was analyzed by the digital expression profiling technology between the H1N1influenza virus infected embryonic mouse and non-infected mouse. The differentially expressed gene were gained and analyzed by semi-quantitative RT-PCR. The consistent semi-quantitative RT-PCR results were obtained:the expression of25genes were consistent with the profiling results, including11up-regulated genes and14down-regulated genes.2. The significantly differentially expression of epigenetic related genes BAF chromatin remodeling complex appeared in infected mouse. We screened BAF chromatin remodeling genes and their downstream Wnt signaling and heart development key infected mouse for further research.3.11differently expression genes in and related to BAF chromatin remodeling were analyzed by semi-quantitative RT-PCR using11.5days pregnancy embryonic hearts. The consistent semi-quantitative RT-PCR results were obtained:the expression of11genes were down-regulated consistent with the profiling results.4. Genes that downstream of Wnt signaling were analyzed by protein expression level. The result showed Sfrp2and Gata4were down-regulated consistent with the profiling results. In this study, the differentially expressed heart related genes and epigenetic genes were selected by the digital expression spectrum screening in the embryonic hearts from the pregnant mice infected with the H1N1influenza virus. BAF chromatin remodeling complex and its downstream Wnt signaling, heart development related genes were down-regulated. BAF chromatin remodeling complex and its signal involved in the development of congenital heart disease. The BAF chromatin remodeling complex and its downstream signal may be an important molecular regulatory pathways in congenital heart disease. The study provided a Preliminary base for molecular mechanisms of environmental factors-mediated congenital heart disease. |
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