Functional Study Of Transcription Factors Runx1 And Tlx3

Both pain and itch are significant sensories that response to the harmful stimulus from the outside environment.Previous studies have reported that transcription factors Runx1 and Tlx3 participated in the development and regulation of sensory neurons.The transcription factor Runx1 can regulate the expression of many sensory ion channels and receptors,and transcription factor Tlx3 plays a decisive role in the terminal differentiation of the precursors of some neurons and the formation of the nerve loop in the posterior brain and spinal cord.In order to further reveal the molecular mechanism in the development of pain and pruritus through the study of the function of Runx1 and Tlx3,and the theoretical basis for the future design of analgesics and antipruritic drugs for specific regulatory links was provided.In this study,we firstly constructed three genotypes mise(Runx1cko,Tlx3 cko,DKO):two conditioned single knockout mise Runx1F/F;Nav1.8-Cre(Runx1cko)and Tlx3F/F;Nav1.8-Cre(Tlx3cko)and a conditioned double knockout mouse Runx1F/F;Tlx3F/F;Nav1.8-Cre(DKO).Then,we explored the roles of the Runx1 and Tlx3 played in the development of pain and pruritus neurons and further explored the relationship between Runx1 and Tlx3 on molecular,cell and animal levels,respectively.These results will provide a theoretical basis for future design of analgesics and antipruritic drugs for specific regulatory links.1.All the three kinds of deficient(Runx1cko,Tlx3 cko,DKO)mice had down regulated expression of most itch related molecules which was regulated by the deletion of Runx1 and Tlx3.2.All the three kinds of deficient(Runx1cko,Tlx3 cko,DKO)mice had weaken acute pruritus and chronic pruritus response which was regulated by the deletion of Runx1 and Tlx3.3.Capsaicin increased the itching response in DKO mice.By injecting AITC or capsaicin into the cheeks of mice,the itching response was significantly enhanced in DKO mice.4.The expression of TRPV1 in DKO mice: the expression of Trpv1 in DKO mice was significantly decreased,but not missing,which was confirmed through the immunofluorescence experiment and RNA in situ hybridization experiment.5.DKO mice had a decreased sensitivity to cold stimulation and inflammatory stimulation.The pain caused by cold stimulation and inflammatory stimulation was meassed by cold plates,Von-Frey,Pinprick,CFA(Complete Freund 's Adjuvant)and SNI(Spared Nerve Injury).