Growth disturbance in fetal liver hematopoiesis of Mll-mutant mice

The MLL (ALL-1, HRX) gene is frequently involved in chromosomal translocations in acute leukemia and has homology with Drosophila trithorax, which controls homeobox gene expression and embryogenesis. To elucidate the function of MII, we generated mice with a mutated MII locus. Mice with a homozygous mutation were embryonic lethal and died at embryonic day 11.5 to 14.5, showing edematous bodies and petechiae. Histological examination revealed that hematopoietic cells were decreased in the liver of homozygous embryos, although they were composed of erythroid, myeloid, monocytic, and megakaryocytic cells with normal differentiation. Colony-forming assays using cells from fetal livers and yolk sacs showed that the number of colonies was markedly reduced and many of the colonies delayed to be recognized in MIImu/mu embryos, although some of the colonies from MIImu/mu embryos developed similarly with that from MII+/+ and MII+/mu embryos, suggesting the delayed onset of the proliferation of hematopoitic precursors. These data show that the hematopoietic precursors were greatly reduced in mutant mice, and suggest that MII functions as a regulator of the growth of hematopoietic precursors. (C) 1998 by The American Society of Hematology.