title: Gimap3 and Gimap5 cooperate to maintain T-cell numbers in the mouse.
abstract: Gimap3 (IAN4) and Gimap5 (IAN5) are highly homologous GTP-binding proteins of the Gimap family. Gimap3 and Gimap5, whose transcripts are abundant in mature lymphocytes, can associate with antiapoptotic Bcl-2 family proteins. While it is established that Gimap5 regulates T-cell survival, the in vivo role of Gimap3 is unclear. Here we report the preparation and characteristics of mouse strains lacking Gimap3 and/or Gimap5. We found that the number of T cells was markedly reduced in mice deficient in both Gimap3 and Gimap5. The defects in T-cell cellularity were more severe in mice lacking both Gimap3 and Gimap5 than in mice lacking only Gimap5. No defects in the cellularity of T cells were detected in mice lacking only Gimap3, whereas bone marrow cells from Gimap3-deficient mice showed reduced T-cell production in a competitive hematopoietic environment. Moreover, retroviral overexpression and short hairpin RNAs-mediated silencing of Gimap3 in bone marrow cells elevated and reduced, respectively, the number of T cells produced in irradiated mice. These results suggest that Gimap3 is a regulator of T-cell numbers in the mouse and that multiple Gimap family proteins cooperate to maintain T-cell survival.
authors: Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima, Japan.
authors: Kouta
authors: K
authors: Yano
authors: Christine
authors: C
authors: Carter
authors: Naofumi
authors: N
authors: Yoshida
authors: Takaya
authors: T
authors: Abe
authors: Akiko
authors: A
authors: Yamada
authors: Takeshi
authors: T
authors: Nitta
authors: Naozumi
authors: N
authors: Ishimaru
authors: Kensuke
authors: K
authors: Takada
authors: Geoffrey W
authors: GW
authors: Butcher
authors: Yousuke
authors: Y
authors: Takahama
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002452:Cell Count; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D020558:GTP Phosphohydrolases / Q000172:deficiency / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: C534135:Gimap5 protein, mouse; C425002:Ian4 protein, mouse; D008565:Membrane Proteins; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins
keywords: Gimap family; Gimap3; Gimap5; Knockout mouse; T-cell survival