Targeting antiapoptotic A1/Bfl-1 by in vivo RNAi reveals multiple roles in leukocyte development in mice
Eleonora Ottina, Francesca Grespi, Denise Tischner, Claudia Soratroi, Stephan Geley, Andreas Ploner, Holger M Reichardt, Andreas Villunger, Marco J Herold
BLOOD | AMER SOC HEMATOLOGY | Published : 2012
Gene-targeting studies in mice have identified the essential roles of most prosurvival Bcl-2 family members in normal physiology and under conditions of stress. The function of one member, Bcl2a1/Bfl-1/A1, is only poorly understood because of quadruplication of its gene locus in mice, hindering conventional knockout studies. To overcome this problem, we generated mouse models allowing traceable constitutive or reversible ablation of A1 in the hematopoietic system by RNA interference. Knockdown of A1 impaired early stages of T-cell differentiation, B-cell homeostasis, and sensitized transitional as well as follicular B cells to apoptosis induced by ligation of the B-cell receptor. As a conseq..View full abstract
Awarded by Graduate School for Molecular Biology and Oncology
Awarded by German Research Council (Deutsche Forschungsgemeinschaft)
Awarded by Deutsche Forschungsgemeinschaft
This work was supported by Graduate School for Molecular Biology and Oncology, (E.O., F.G., A.V., and S.G.; and SFB021, A.V.), the Austrian Science Fund, the Tiroler Krebshilfe (E.O. and D.T.), and the German Research Council (Deutsche Forschungsgemeinschaft, Re 1631/7-1; H.M.R.). M.J.H. was supported by the Deutsche Forschungsgemeinschaft (postdoctoral fellowship He 5740/1-1).