The Study Of The Role Of BMP4 In Mouse Neural Tube Defects

ObjectiveThe present experiment aims to build NTDs mouse model induced by ATRA and study the effect of the interaction between BMP4 and its receptors and BMPs signaling on the development of NTDs, therefore to explore the possible molecular mechanism of BMP4 on the formation of NTDs induced by ATRA.MethodsHealthy adult mice of Kunming breed were selected and provided with a feed of 50mg/kg ATRA at E7.25-7.5d, which induced the establishment of NTDs mouse model, and examined the malformation of fetus by naked eye and anatomical microscope. RT-PCR technology and in situ hybridization were adopted to examine the expression of genes in neutral tube structure at different growth stages of neutral tubes, Western-blot was performed to examine the expression of key signaling protein, based on which a comprehensive analysis was conducted. Results1. Excessive ATRA plays a significant role in embryo teratogenicity, which results uterus of pregnancy mice obviously hyperaemia and various NTDs (anencephalia and spina bifida).2. The expression of BMP4 mRNA in control and experimental fetus neutral tubes depends on time and falls with time, BMPRIA mRNA steadly increases, while BMP RIB first increases behind intense decline during experimental neural tube closure. Overall expression of BMPRII are always stable, and that of experimental group is higher than control group.3. During key point of neural tube closure, BMP4mRNA expressed in dorsal neural epithelia and of that of the experimental group tends to be higher than control group, as signaling molecules specific for the BMPs pathway, phosphorylated Smadl level is increased, which in experimental group is higher than that of control group, while Smad6 present opposite tendency.Conclusions1. NTDs mouse model of Kunming breed was successfully built induced by ATRA, which makes perfect model foundation for the study of pathogeny of NTDs.2. BMP4 possiblely induces cell apoptosis during embryo neural tube closure, the roles of receptor I and II of BMP4 in inducing NTDs are not to be neglected, they are probably major factors involved in molecule regulation during the occurrence of NTDs.3. Excessive ATRA probably causes the increase of expression level of BMP4 mRNA through ATRA receptors, which interferes Smad signaling pathways, promotes the rate of cell apoptosis higher to result in NTDs.