The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/4/1467/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 8, April 21, 1997 1467-1480

Article

Impairment of T Cell Development in {delta}EF1 Mutant Mice

Yujiro Higashi*, Hiroki Moribe*, Tsuyoshi Takagi*, Ryohei Sekido*, Kiyoshi Kawakami{ddagger}, Hitoshi Kikutani*, and Hisato Kondoh*

From the * Institute for Molecular and Cellular Biology, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565, Japan; {ddagger} Department of Biology, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi-machi, Kawachi-gun, Tochigi 329-04, Japan

Using the method of gene targeting in mouse embryonic stem cells, regulatory function of {delta}EF1, a zinc finger and homeodomain-containing transcription factor, was investigated in vivo by generating the {delta}EF1 mutant mice. The mutated allele of {delta}EF1 produced a truncated form of the {delta}EF1 protein lacking a zinc finger cluster proximal to COOH terminus. The homozygous {delta}EF1 mutant mice had poorly developed thymi with no distinction of cortex and medulla. Analysis of the mutant thymocyte showed reduction of the total cell number by two orders of magnitude accompanying the impaired thymocyte development. The early stage intrathymic c-kit+ T precursor cells were largely depleted. The following thymocyte development also seemed to be affected as assessed by the distorted composition of CD4- or CD8-expressing cells. The mutant thymocyte showed elevated {alpha}4 integrin expression, which might be related to the T cell defect in the mutant mice. In the peripheral lymph node tissue of the mutant mice, the CD4–CD8+ single positive cells were significantly reduced relative to CD4+CD8– single positive cells. In contrast to T cells, other hematopoietic lineages appeared to be normal. The data indicated that {delta}EF1 is involved in regulation of T cell development at multiple stages.

Address correspondence to Yujiro Higashi, Institute for Molecular and Cellular Biology, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565, Japan.

1 Abbreviations used in this paper: DN, double negative; DP, double positive; d.p.c., days post coitum; FITC, fluorescein isothiocyanate; HBS, Hepes-buffered saline; SP, single positive.


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