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© The Rockefeller University Press, 0022-1007/1997/9/877/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 6, September 15, 1997 877-885

Articles

Two Distinct Steps during Thymocyte Maturation from CD4–CD8– to CD4+CD8+ Distinguished in the Early Growth Response (Egr)-1 Transgenic Mice with a Recombinase-activating Gene–Deficient Background

Toru Miyazaki

From the Basel Institute for Immunology, Postfach CH-4005, Basel, Switzerland

The early growth response (Egr)-1 is a zinc finger–containing transcription factor belonging to the immediate–early genes. Its expression in CD4/CD8 double negative (DN) immature thymocytes suggests that Egr-1 expression may be involved in early thymocyte development. In transgenic mice overexpressing Egr-1 in a recombinase-activating gene–deficient background, thymocytes bypassed the block at the CD25+CD44– DN stage and matured to the immature CD8 single-positive (ISP) cell stage, but not further to the CD4/CD8 double-positive (DP) cell stage. When these mice were irradiated, thymocytes did develop to the DP stage, suggesting transcriptional induction of additional genes by irradiation that are required to promote thymocyte development from the ISP to the DP stage. These results provide genetic evidence for two distinct steps during early thymocyte development from the CD25+CD44– DN to the DP stage. The first step, from the CD25+CD44– DN to the ISP stage, can be entirely promoted by overexpression of Egr-1.

Address correspondence to Toru Miyazaki, Basel Institute for Immunology, Grenzacherstrasse 487, Postfach CH-4005, Basel, Switzerland. Phone: 41-61-605-1294; FAX: 41-61-605-1364; E-mail: miyazaki{at}bii.ch

The author thanks U. Müller for microinjection; Drs. K.S. Campbell, M. Colonna, S. Gilfillan, H.J. Fehling, and M. Bogue (Baylor College of Medicine, Waco, TX) for critical reading of the manuscript; E. Wagner, W. Metzger, and R. Zedi for help with the mice; and M. Dessing for help with the cell sorting and cell cycle analysis.

Basel Institute for Immunology was founded and is supported by F. Hoffmann-La Roche Ltd. (Basel, Switzerland).

1 Abbreviations used in this paper: DN, double negative; DP, double-positive; Egr, early growth response; hGH, human growth hormone; HSA, heat-stable antigen; ISP, immature CD8 single-positive; NL, negative littermates; RAG, recombinase-activating gene; RT-PCR, reverse transcriptase PCR; Tg, transgenic.


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