Lack of natural killer cell precursors in fetal liver of Ikaros knockout mutant mice

The role of Ikaros in early stages of natural killer (NK) cell differentiation was investigated using an in vitro system that promotes proliferation and differentiation of NK cell precursors into mature NK1.1+ cells. Day 14.5 fetal liver cells from mice, either homozygous for Ikaros Null or dominant negative (DN) mutations, had severe 55- to 79-fold reductions in functional NK cell precursors. Although there was no statistically significant difference between values for + /+ and +/- Null mice, the mean precursor frequency for DN mutant (+/-) mice was significantly above that for DN -/- mice and below that for DN +/+ mice. The NK activity values for cells generated from the NK cell precursors followed the same respective relationships found for NK cell precursor frequencies. These data suggest that the deficiency of mature NK cells in Ikaros mutant mice is related to lack of functional precursors.