title: Generation and characterisation of mice deficient in the multi-GTPase domain containing protein, GIMAP8.
abstract: BACKGROUND
  GTPases of the immunity-associated protein family (GIMAPs) are predominantly expressed in mature lymphocytes. Studies of rodents deficient in GIMAP1, GIMAP4, or GIMAP5 have demonstrated that these GTPases regulate lymphocyte survival. In contrast to the other family members, GIMAP8 contains three potential GTP-binding domains (G-domains), a highly unusual feature suggesting a novel function for this protein. To examine a role for GIMAP8 in lymphocyte biology we examined GIMAP8 expression during lymphocyte development. We also generated a mouse deficient in GIMAP8 and examined lymphocyte development and function.
  
  
  RESULTS
  We show that GIMAP8 is expressed in the very early and late stages of T cell development in the thymus, at late stages during B cell development, and peripheral T and B cells. We find no defects in T or B lymphocyte development in the absence of GIMAP8. A marginal decrease in the number of recirculating bone marrow B cells suggests that GIMAP8 is important for the survival of mature B cells within the bone marrow niche. We also show that deletion of GIMAP8 results in a delay in apoptotic death of mature T cell in vitro in response to dexamethasone or γ-irradiation. However, despite these findings we find that GIMAP8-deficient mice mount normal primary and secondary responses to a T cell dependent antigen.
  
  
  CONCLUSIONS
  Despite its unique structure, GIMAP8 is not required for lymphocyte development but appears to have a minor role in maintaining recirculating B cells in the bone marrow niche and a role in regulating apoptosis of mature T cells.
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, United Kingdom.
authors.forename: Louise M C
authors.initials: LM
authors.lastname: Webb
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, United Kingdom.
authors.forename: John C
authors.initials: JC
authors.lastname: Pascall
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, United Kingdom.
authors.forename: Lucy
authors.initials: L
authors.lastname: Hepburn
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, United Kingdom.
authors.forename: Christine
authors.initials: C
authors.lastname: Carter
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Turner
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, United Kingdom.
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Butcher
mesh_terms: D000818:Animals; D017209:Apoptosis; D020558:GTP Phosphohydrolases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: C506126:GIMAP8 protein, mouse; D020558:GTP Phosphohydrolases