Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities.

Abstract

PU.1 is a member of the ets family of transcription factors and is expressed exclusively in cells of the hematopoietic lineage. Mice homozygous 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 cells, 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 undetectable in these older mice. Within the myeloid lineage, despite a lack of macrophages in the older antibiotic‐treated animals, a few cells with the characteristics of neutrophils began to appear by day 3. While the PU.1 protein appears not to be essential for myeloid and lymphoid lineage commitment, it is absolutely required for the normal differentiation of B cells and macrophages.

Neuroinflammation: Ways in Which the Immune System Affects the Brain

“…Microglia belong to the hematopoietic lineage, as evidenced by microglia loss in Pu.1 knockout mice, which lack a transcription factor required specifically in hematopoietic cells [14]. Microglia progenitors enter the CNS at embryonic day 9.5-10.5 [1,2], prior to the emergence and differentiation of other nervous system glial-cell types, and consistent with their critical role in shaping CNS development.…”

GOOSECOID inhibits erythrocyte differentiation by competing with Rb for PU.1 binding in murine cells

“…One strain of PU.1 knock out mice shows defects in erythroid maturation (Scott et al, 1994). Another PU.1 de®cient mouse strain exhibits no apparent defects in erythrocyte development but are de®cient in macrophages, neutrophils, B cells, and T cells compared to wild-type mice (McKercher et al, 1996;Scott et al, 1997). In both strains, however, the Nterminal half of the PU.1 gene is intact in the targeted genome, and in neither case has it been determined whether the N-terminal peptide is expressed.…”

Spi-1 transgenic mice develop a clonal erythroleukemia which does not depend on p53 mutation

“…Spi-1/PU.1 plays an essential role in normal lymphopoiesis and myelopoiesis. It regulates the transcription of many myeloid and B lymphoid genes (for review Moreau-Gachelin, 1994) and its inactivation in mice results in a multilineage defect characterized by an absence of B lymphocytes and macrophages (McKercher et al, 1996;Scott et al, 1997). Although the down regulation of spi-1 during the chemicallyinduced di erentiation of Friend cells suggested that Spi-1 was involved in the di erentiation arrest of the proerythroblast (Schuetze et al, 1992), the role of Spi-1/PU 1 in the transformation of erythroid cells was deduced from the pathology observed in mice overexpressing a spi-1 transgene (Moreau-Gachelin et al, 1996).…”