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

Scott R. McKercher, Bruce E. Torbett, Karen L. Anderson, Gregory W. Henkel, Deborah J. Vestal, Helene Baribault, Michael Klemsz, Ann J. Feeney, Gillian E. Wu, Christopher J. Paige, Richard A. Maki

Research output: Contribution to journalArticle

853 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5647-5658
Number of pages12
JournalEMBO Journal
Volume15
Issue number20
StatePublished - Oct 15 1996

    Fingerprint

Keywords

  • ets family
  • Hematopoiesis
  • PU.1
  • Transcription factor

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

McKercher, S. R., Torbett, B. E., Anderson, K. L., Henkel, G. W., Vestal, D. J., Baribault, H., Klemsz, M., Feeney, A. J., Wu, G. E., Paige, C. J., & Maki, R. A. (1996). Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities. EMBO Journal, 15(20), 5647-5658.