| First Author | Brewer JA | Year | 2002 |
| Journal | J Immunol | Volume | 169 |
| Issue | 3 | Pages | 1309-18 |
| PubMed ID | 12133953 | Mgi Jnum | J:98328 |
| Mgi Id | MGI:3577990 | Doi | 10.4049/jimmunol.169.3.1309 |
| Citation | Brewer JA, et al. (2002) Green fluorescent protein-glucocorticoid receptor knockin mice reveal dynamic receptor modulation during thymocyte development. J Immunol 169(3):1309-18 |
| abstractText | To delineate the cellular targets and mechanisms by which glucocorticoids (GCs) exert their actions, we generated mice in which a green fluorescent protein (GFP)-GC receptor (GR) fusion gene is knocked into the GR locus. In these mice, the GFP-GR protein, which is functionally indistinguishable from endogenous GR, allows the tracking and quantitation of GR expression in single living cells. In GFP-GR thymus, GR expression is uniform among embryonic thymocyte subpopulations but gradually matures over a 3-wk period after birth. In the adult, GR is specifically induced to high levels in CD25(+)CD4(-)CD8(-) thymocytes and returns to basal levels in CD4(+)CD8(+) thymocytes of wild-type and positively selecting female HY TCR-transgenic mice, but not negatively selecting male HY TCR-transgenic mice. In GFP-GR/recombinase-activating gene 2(-/-) thymocytes, GR expression is down-regulated by pre-TCR complex stimulation. Additionally, relative GR expression is dissociated from GC-induced apoptosis in vivo. Results from these studies define differential GR expression throughout ontogeny, suggest pre-TCR activation as a specific mechanism of GR down-regulation, define immature CD8(+) thymocytes as novel apoptosis-sensitive GC targets, and separate receptor abundance from susceptibility to apoptosis across thymocyte populations. |
