Putative GTPase GIMAP1 is critical for the development of mature B and T lymphocytes

Saunders, Amy and Webb, Louise M C and Janas, Michelle L and Hutchings, Amanda and Pascall, John and Carter, Christine and Pugh, Nicholas and Morgan, Geoff and Turner, Martin and Butcher, Geoffrey W (2010) Putative GTPase GIMAP1 is critical for the development of mature B and T lymphocytes. Blood, 115 (16). pp. 3249-57. ISSN 0006-4971

Abstract

The guanosine triphosphatases (GTPases) of the immunity-associated protein (GIMAP) family of putative GTPases has been implicated in the regulation of T-lymphocyte development and survival. A mouse conditional knockout allele was generated for the immune GTPase gene GIMAP1. Homozygous loss of this allele under the influence of the lymphoid-expressed hCD2-iCre recombinase transgene led to severe (> 85%) deficiency of mature T lymphocytes and, unexpectedly, of mature B lymphocytes. By contrast there was little effect of GIMAP1 deletion on immature lymphocytes in either B or T lineages, although in vitro studies showed a shortening of the survival time of both immature and mature CD4(+) single-positive thymocytes. These findings show a vital requirement for GIMAP1 in mature lymphocyte development/survival and draw attention to the nonredundant roles of members of the GIMAP GTPase family in these processes.