Impairment of T cell development in deltaEF1 mutant mice

Y Higashi, H Moribe, T Takagi, R Sekido, K Kawakami, H Kikutani, H Kondoh

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

Using the method of gene targeting in mouse embryonic stem cells, regulatory function of deltaEF1, a zinc finger and homeodomain-containing transcription factor, was investigated in vivo by generating the deltaEF1 mutant mice. The mutated allele of deltaEF1 produced a truncated form of the deltaEF1 protein lacking a zinc finger cluster proximal to COOH terminus. The homozygous deltaEF1 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 alpha4 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 deltaEF1 is involved in regulation of T cell development at multiple stages.

Original languageEnglish
Pages (from-to)1467-79
Number of pages13
JournalJournal of Experimental Medicine
Volume185
Issue number8
Publication statusPublished - 21 Apr 1997

Keywords

  • Animals
  • Antigens, CD
  • Antigens, CD44
  • Cell Differentiation
  • DNA-Binding Proteins
  • Gene Expression
  • Homeodomain Proteins
  • Immunophenotyping
  • Integrin alpha4
  • Lymph Nodes
  • Lymphocyte Count
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nuclear Proteins
  • Receptors, Interleukin-2
  • Spleen
  • Structure-Activity Relationship
  • T-Lymphocytes
  • Thymus Gland
  • Transcription Factors
  • Zinc Fingers

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  • Cite this

    Higashi, Y., Moribe, H., Takagi, T., Sekido, R., Kawakami, K., Kikutani, H., & Kondoh, H. (1997). Impairment of T cell development in deltaEF1 mutant mice. Journal of Experimental Medicine, 185(8), 1467-79. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196278/