REQUIREMENT OF TRANSCRIPTION FACTOR PU.1 IN THE DEVELOPMENT OF MULTIPLE HEMATOPOIETIC LINEAGES

The transcription factor PU.1 is a hematopoietic-specific member of th e ets family. Mice carrying a mutation in the PU.1 locus were generate d by gene targeting. Homozygous mutant embryos died at a late gestatio nal stage. Mutant embryos produced normal numbers of megakaryocytes an d erythroid progenitors, but some showed an impairment of erythroblast maturation. An invariant consequence of the mutation was a multilinea ge defect in the generation of progenitors for B and T lymphocytes, mo nocytes, and granulocytes. Thus, the developmental programs of lymphoi d and myeloid lineages require a common genetic function likely acting at the level of a multipotential progenitor.