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J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/04/1467/14 $2.00
Volume 185, Number 8, April 21, 1997 1467-1480

Impairment of  T Cell Development in delta EF1 Mutant Mice

By Yujiro Higashi,* Hiroki Moribe,* Tsuyoshi Takagi,* Ryohei Sekido,* Kiyoshi Kawakami,Dagger Hitoshi Kikutani,* and Hisato Kondoh*

From the * Institute for Molecular and Cellular Biology, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565, Japan; Dagger  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.


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