Generation And Phenotypic Characterization Of Mesenchyme-specific Knockout Mice Of The Zinc Finger Protein ZBTB20

Zinc finger protein ZBTB20,also known as the Dendritic cell-derived POZ zinc finger protein(DPZF),is one of the members of the family of BTB zinc finger protein.It is important for the body growth and development as a kind of transcription factors.To our knowledge,ZBTB20 were highly expressed in pancreas,liver,hippocampus,heart and other organs.It is crucial in regulation of islet B cell function,expression of alpha fetoprotein(AFP)and monitory effect on pain perception.We have found several serous phenotype in ZBTB20 knockout mice,including the postnatal growth retardation,lethality,hippocampus and heart developmental disorders,metabolism disorders and hematopoietic dysfunction.ZBTB20 gene mutations in the crowd can cause the Primrose syndrome,characterized by abnormal bone development,mental retardation,special features such as multiple system symptoms.However,the study about ZBTB20 in physiological function is not perfect.ZBTB20 role in various tissues and organs has not been fully elucidated and the function about ZBTB20 in mesenchymal cells remain to be established.Mesenchymal stem cells,as one of pluripotent stem cells of embryonic mesoderm,named after its ability of differentiation into interstitial tissue.Under the specific environment in vivo and in vitro,they can be induced into cartilage,bone,fat,ligaments,muscles,tendons,nerves and endothelial cells.Since highly expression of ZBTB20 in mesenchymal cells,its strong regulatory mechanism is underlying of the differentiation and development.Objective:To clarify the function of ZBTB20 in mesenchymal cells,and perfect it's physiological function.Methods: By using gene targeting technology,we establish the terms of mesenchymal cells specificity knockout mice model(ZBTB20F/F / Prrx1-Cre)for the first time,and this provides us with convenient conditions to clarify the ZBTB20 function in mesenchymal cells.ZBTB20 express in the body generally appear in the embryo 13.5 to 14.5 days while Prrx1-Cre tools of Cre activity in embryonic day(E9.5)9.5 begin to express which makes it possible build mesenchymal cells specificity knockout mice model.Prrx1-Cre transgenic mice provides effective means in the process of gene regulation about limbs for research related development,and limbs germ has always been important model of growth and development of vertebrates.Results : According to the preliminary research of genotype of the model,we found that MC-ZB20 KO mice do not show any significant changes in growth and development in a certain period of time.Within 4 months of age,we did not observe any obvious difference in this model in development indexes compared with control group,such as weight,body length,the content of the fat,the survival and fertility rate,hair growth,bone growth,pituitary development,but have changed in glycemic metabolism.The other way,by observing mice at the age of 6 months or elder,we found that gradually obvious skeletal dysplasia with age,increasing hardening of the palm and toe joint,spine curved,disabilities of activity and significantly decrease in Fertility rate of MC-ZB20 KO mice.Conclusion: Here we show that ZBTB20 in mesenchymal cells have a certain degree of regulation in growth and development,especially in the regulation of limb bone development,and it is conducive to maintaining blood sugar balance.