TARGETED DISRUPTION OF THE PU.1 GENE RESULTS IN MULTIPLE HEMATOPOIETIC ABNORMALITIES

PU.1 is a member of the ets family of transcription factors and is exp ressed exclusively in cells of the hematopoietic lineage, Mice homozyg ous for a disruption in the PU.1 DNA binding domain are born alive but die of severe septicemia within 48 h, The analysis of these neonates revealed a lack of mature macrophages, neutrophils, B cells and T cell s, although erythrocytes and megakaryocytes were present. The absence of lymphoid commitment and development in null mice was not absolute, since mice maintained on antibiotics began to develop normal appearing T cells 3-5 days after birth, In contrast, mature B cells remained un detectable in these older mice, Within the myeloid lineage, despite a lack of macrophages in the older antibiotic-treated animals, a few cel ls with the characteristics of neutrophils began to appear by day 3, W hile the PU.1 protein appears not to be essential for myeloid and lymp hoid lineage commitment, it is absolutely required for the normal diff erentiation of B cells and macrophages.