Gene structure and chromosomal assignment of mouse GITR, a member of the tumor necrosis factor/nerve growth factor receptor family

GITR is a type I transmembrane protein that belongs to the tumor necrosis f actor/nerve growth factor receptor (TNF/NGFR) family. This receptor is pref erentially expressed in activated T lymphocytes and may function as signali ng molecule during T-cell development. In the present study, we examined th e genomic organization of the entire mouse GITR (mGITR) gene. The gene span s a 2543-bp region and consists of five exons (with a length ranging from 8 8 bp to 395 bp) and four introns (67 bp to 778 bp), In agreement with GITR expression in activated T cells, consensus elements for transcription facto rs involved in T-cell development and activation were identified in the 5' flanking region, including a consensus element for NF-kappa B, Two highly s ignificant binding sites for MyoD and one binding site for myogenin were al so found, suggesting involvement of GITR in muscle development. The mGITR g ene contains 17 transcription initiation sites distributed over a 76-bp reg ion, all used with the same frequency. We localized mGITR to the murine chr omosome 4 (E region), where other 4 TNF/NGFR members localize, including m4 -1BB and mOX40. These results further indicate that GITR shares several fea tures with OX40, 4-1BB, and CD27, suggesting the existence of a new subfami ly of the TNFR family, as also confirmed by the similarity of their cytopla smic domains.