The Role And Mechanism Of Arrb1 In T-cell Development In Mices

Objective: Normal T cells are derived from bone marrow hematopoietic stem cells(HSCs)and migrate to the thymus to develop into primary T cells.It is noted that the entire development process is complex and highly ordered.The entire development process is complex and highly ordered.Abnormal developmental processes,such as T-cell developmental arrest,are highly prone to human T cell acute lymphoblastic leukemia(TALL).Previous shudies have demonstrated that the Arrb1(?-arrestin1)gene deficiency affects the early hematopoietic function of zebrafish.Remarkably,Arrb1 is an important molecule that favors the progressive emergence of T-ALL.Here we detected the proportion of bone marrow hematopoietic cells and the composition of T cells in thymus development stages in Arrb1 knockout mice.And accordingly,the investigation of the possible mechanism led us to provide an experimental basis and lay foundation for further investigation of the pathogenesis of T-ALL.Methods: The expression of Arrb1 was detected by q-PCR and Western Blot respectively in Arrb1 knockout mice.HE staining was used to detect the morphological changes in bone marrow and thymus in Arrb1 knockout mice.Cell suspensions were prepared from the bone marrow,thymus of Arrb1 knockout and wild-type mice.HSC,lymphoid-primed multipotential progenitors(LMPP),common lymphoid progenitors(CLP),common myeloid progenitors(CMP),granulocyte–monocyte progenitors(GMP),megakaryocyte–erythrocyte progenitors(MEP),T-cell were detected by flow cytometry.CD4CD8 double negative(DN)cells were sorted by flow cytometry,the expression of developmental-related genes Tal1,Runx1 was detected by q-PCR and Western Blot.Results: Compared with the wild-type mice,there was no pathological change in the bone marrow and thymus of Arrb1 gene knockout mice.The proportions of HSC,LMPP,CLP,CMP,GMP,and MEP in the bone marrow did not change significantly,the proportion of thymus CD4CD8 DN cells increased significantly(P <0.05),the proportion of CD4CD8 DP cells was significantly decreased(P<0.05),the expression of mRNA and protein levels of Tal1 and Runx1 were increased(P<0.05).Conclusion: Taken together,these results findings indicated that sustained Arrb1 deficiency perturbs the development of T lymphocytes,which led to T lymphocytes arrest in DN stage,suggesting that Arrb1 might be important,particular in T-ALL progression.