PU.1 and hematopoiesis: Lessons learned from gene targeting experiments
Abstract
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 role 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 neutrophil 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.
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PU.1−/− mice do not produce mature macrophages and have very few granulocytes.
“PU.1 2 / 2 mice do not produce mature macrophages and have very few granulocytes. (60)”
From Review: ICSBP/IRF-8: Its Regulatory Roles in the Development of Myeloid Cells (2002) · cites this paper as [60]
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- Authors
- Simon, M. C.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Simon, M.Celeste
- ORCID
- Simon, M.Celeste
- Venue
- Seminars in Immunology
- Publisher
- Elsevier BV
- Published
- 1998-04
- Volume
- 10
- Issue
- 2
- Pages
- 111-118
- ISSN
- 1044-5323 (ISSN-L)
- OpenAlex
- W2053470080
- Cited by
- 42
- References
- 0
- Citations by year
- 2022: 1 · 2020: 1 · 2019: 1 · 2015: 1 · 2013: 1
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Seminars in Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- PU.1, hematopoiesis, hematopoietic transcription factors, gene targeting, allelic series, B cell development, T cell development, monocyte development, neutrophil development, yolk sac hematopoiesis, fetal liver hematopoiesis, bone marrow hematopoiesis
- MeSH terms
- Proto-Oncogene Protein Spi-1, Animals, Hematopoiesis, Humans, Proto-Oncogene Proteins, Trans-Activators, Gene Targeting, Mice
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