Abstract
Abstract The X chromosome linked RNA helicase DDX3X plays numerous roles in regulation of cellular RNA metabolism and immune responses. Loss of function mutations in this helicase are linked to neurological disease and malignancies, including NK/T-cell lymphoma. To investigate how DDX3X contributes to development of NK cells, we generated mice with a conditional deletion Ddx3x in Ncr1-expressing cells. Female mice with homozygous deletion of NK cells exhibit a complete loss of NK cells. By comparison, the frequency of NK cells was significantly reduced in hemizygous male mice. The reduction in NK cells is associated with increased apoptosis in this lineage early during differentiation in the bone marrow. Our ongoing work is focused on elucidation of the mechanisms by which DDX3X regulates NK cell survival, differentiation, and malignant transformation, as well as on the capacity of DDX3Y to compensate for loss of DDX3X in hemizygous male mice. Our data identify a novel role for DDX3 RNA helicases in the development and survival of NK cells in mice.