G imap3 and G imap5 cooperate to maintain T ‐cell numbers in the mouse

G imap3 ( IAN 4) and G imap5 ( IAN 5) are highly homologous GTP ‐binding proteins of the G imap family. G imap3 and G imap5, whose transcripts are abundant in mature lymphocytes, can associate with antiapoptotic B cl‐2 family proteins. While it is established that G imap5 regulates T ‐cell survival, the in vivo role of G imap3 is unclear. Here we report the preparation and characteristics of mouse strains lacking G imap3 and/or G imap5. We found that the number of T cells was markedly reduced in mice deficient in both G imap3 and G imap5. The defects in T ‐cell cellularity were more severe in mice lacking both G imap3 and G imap5 than in mice lacking only G imap5. No defects in the cellularity of T cells were detected in mice lacking only G imap3, whereas bone marrow cells from G imap3‐deficient mice showed reduced T ‐cell production in a competitive hematopoietic environment. Moreover, retroviral overexpression and short hairpin RNA s‐mediated silencing of G imap3 in bone marrow cells elevated and reduced, respectively, the number of T cells produced in irradiated mice. These results suggest that G imap3 is a regulator of T ‐cell numbers in the mouse and that multiple G imap family proteins cooperate to maintain T ‐cell survival.