PU.1 and hematopoiesis: Lessons learned from gene targeting experiments

The advent of gene targeting technology in mouse embryonic stem cells has revolutionized the study of the development of organ systems in mammals. Hematopoietic transcription factors play a critical role in blood cell development. Targeted mutagenesis of the murine PU.1 locus has revealed the pivotal rob this protein plays in blood cell differentiation at all stages of hematopoiesis (yolk sac, fetal liver and bone marrow). PU.1 has been disrupted by two independent research groups and both strains of PU.1-deficient mice exhibit abnormalities in B cell, T cell, monocyte and ne rt trophil development. The independent mutations have yielded some differences in phenotype suggesting that the different strategies for gene targeting have resulted in the beginning of an 'allelic series' at the PU.1 locus. Both strains of PU.1(-/-) mice provide exciting reagents for future study of the role of this factor in blood lineage specification.