The Effect Of MarvelD1 Gene Knockout On Spleen Structure And T-cell Subpopulation In Mice

MarvelD1(MARVEL domain containing 1)is a functional gene discovered by previous research group in our laboratory.The gene expression analysis results showed that MarvelD1 expression was significantly down-regulated,and its promoter region was hypermethylated in multiple malignant tumors and cancer cells.Therefore,MarvelD1 gene is considered as a potential tumor suppressor gene.In recent years,with the deepening of research,the cognition of MarvelD1 gene function has been expanding.Previous study demonstrated that MarvelD1 isn’t only inhibiting the development of tumor,but also affects tumor invasion and metastasis by regulating the expression balance of ITGB1 and ITGB4.In addition,MarvelD1 gene knockout mice also show that MarvelD1 plays an important role in the development of neural differentiation in brain tissue and plays a key role in the regulation of endodermal organ development.In addition to the above known biological functions,furthermore,the oxidative stress mouse model was constructed in the preliminary research,it was observed that the splenic weight of MarvelD1 gene knock-out aged mice was significantly reduced after oxidative stress stimulation as compared with the wild-type mice.More importantly,the test results of oxidative stress markers suggested that the levels of8-hydroxydeoxyguanosine and malondialdehyde in splenic tissue of MarvelD1knockout mice were significantly higher than those in the wild-type group,and the differences were more significant after oxidative stress stimulation.As it is well-known that the spleen plays an important role in the immune system of the body,and has hematopoietic and blood filtration functions,so it is closely related to the health status of the body.Therefore,in this study,we used MarvelD1 knockout mice as the main research object to explore the influences of MarvelD1 knockout on the structure and function of the spleen in mice.The results showed that MarvelD1 knockout mice were more sensitive to stress stimulation than wild-type mice,and the structure and t-cell number of spleen in the MarvelD1 knockout mice were significantly different from wild-type mice after oxidative stress stimulation.To further explore whether MarvelD1 gene knockout influenced splenic development in mice at different time points.The spleen index,the number of T lymphocyte subsets and the proportion balance of mice were analyzed.The statistical analysis of spleen index showed that there was no significant difference in spleen index between the two genotypes of mice at different development time.However,it is worth noting that the FCM analysis results showed that the number of CD8~+T cells was significantly higher than that of MarvelD1 wild-type mice,which suggested that MarvelD1 might affect the number and proportion balance of t-cell subgroups in spleen of MarvelD1 knockout mice.In order to further clarify that MarvelD1 knockout could altered structure and T lymphocyte subsets of spleen in the mice,as well as the influence on immune function,for that we utilized MarvelD1 knockout and wild-type mice were infected by listeria intraperitoneally in this study.Flow cytometry.The results showed that the number of CD8~+T cells in MarvelD1 knockout mice increased significantly after listeria infection,which was significantly different from wild-type mice.In addition,the results of real-time quantitative PCR indicated that MarvelD1 expression of immune-related cytokines were higher in MarvelD1 knockout mice than in wild-type mice.In conclusion,we found that MarvelD1 knock-out affected the splenic structure and the proportional balance of the t-lymphocyte subpopulation of the main immune function cells in mice,and MarvelD1 was strongly correlated with the expression of inflammatory factors in response to infection stimulation.This suggests that MarvelD1may have an important influence on immune function,and its regulatory molecular mechanism needs further exploration.