Immunology Programme, The Babraham Institute, Cambridge, UK.
Blood. 2010 Apr 22;115(16):3249-57. doi: 10.1182/blood-2009-08-237586. Epub 2010 Mar 1.
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.
免疫相关蛋白(GIMAP)家族的鸟嘌呤三磷酸酶(GTPases)已被牵涉到 T 淋巴细胞发育和存活的调控中。免疫 GTP 酶基因 GIMAP1 的小鼠条件性敲除等位基因已被生成。在淋巴样表达的 hCD2-iCre 重组酶转基因的影响下,该等位基因的纯合缺失导致成熟 T 淋巴细胞(超过 85%)和成熟 B 淋巴细胞严重缺乏。相比之下,GIMAP1 缺失对 B 或 T 谱系中的未成熟淋巴细胞几乎没有影响,尽管体外研究表明,不成熟和成熟的 CD4(+)单阳性胸腺细胞的存活时间都缩短了。这些发现表明 GIMAP1 在成熟淋巴细胞发育/存活中是必需的,并引起人们对 GIMAP GTPase 家族成员在这些过程中的非冗余作用的关注。