IMPAIRMENT OF T-CELL DEVELOPMENT IN DELTA-EF1 MUTANT MICE

Using the method of gene targeting in mouse embryonic stem cells, regu latory function of delta EF1, a zinc finger and homeodomain-containing transcription factor, was investigated in vivo by generating the delt a EF1 mutant mice. The mutated allele of delta EF1 produced a truncate d form of the delta EF1 protein lacking a zinc finger cluster proximal to COOH terminus. The homozygous delta EF1 mutant mice had poorly dev eloped thymi with no distinction of cortex and medulla. Analysis of th e mutant thymocyte showed reduction of the total cell number by two or ders of magnitude accompanying the impaired thymocyte development. The early stage intrathymic c-kit(+) T precursor cells were largely deple ted. 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, wh ich might be related to the T cell defect in the mutant mice. In the p eripheral lymph node tissue of the mutant mice, the CD4(-)CD8(+) singl e positive cells were significantly reduced relative to CD4(+)CD8(-) s ingle positive cells. In contrast to T cells, other hematopoietic line ages appeared to be normal. The data indicated that delta EF1 is invol ved in regulation of T cell development at multiple stages.