Basis of hematopoietic defects in platelet-derived growth factor (PDGF)-B and PDGF β-receptor null mice
Abstract
Platelet-derived growth factor (PDGF)-B and PDGF beta-receptor (PDGFR beta) deficiency in mice is embryonic lethal and results in cardiovascular, renal, placental, and hematologic disorders. The hematologic disorders are described, and a correlation with hepatic hypocellularity is demonstrated. To explore possible causes, the colony-forming activity of fetal liver cells in vitro was assessed, and hematopoietic chimeras were demonstrated by the transplantation of mutant fetal liver cells into lethally irradiated recipients. It was found that mutant colony formation is equivalent to that of wild-type controls. Hematopoietic chimeras reconstituted with PDGF-B(-/-), PDGFR beta(-/-), or wild-type fetal liver cells show complete engraftment (greater than 98%) with donor granulocytes, monocytes, B cells, and T cells and display none of the cardiovascular or hematologic abnormalities seen in mutants. In mouse embryos, PDGF-B is expressed by vascular endothelial cells and megakaryocytes. After birth, expression is seen in macrophages and neurons. This study demonstrates that hematopoietic PDGF-B or PDGFR beta expression is not required for hematopoiesis or integrity of the cardiovascular system. It is argued that metabolic stress arising from mutant defects in the placenta, heart, or blood vessels may lead to impaired liver growth and decreased production of blood cells. The chimera models in this study will serve as valuable tools to test the role of PDGF in inflammatory and immune r…
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The E2F network as well as the Cdk1 and Cdk2 related pathways are associated with anemia, the most prominent and consistent clinical sign of trypanosome infection.
“The E2F network as well as the Cdk1 and Cdk2 related pathways are also associated with anemia which is the most prominent and consistent clinical sign of trypanosome infection (Kaminski et al., 2001; Dimova and Dyson, 2005; Noyes et al., 2011, Hu and Sun, 2016).”
From Identification of Candidate Signature Genes and Key Regulators Associated With Trypanotolerance in the Sheko Breed (2019) · cites this paper as Kaminski et al., 2001
The PDGFB → STATs pathway is involved in anemia.
“In addition, knock-out mice for PDGF-B develop anemia (Kaminski et al., 2001) which indicates that the PDGFB –> STATs pathway is also involved in this disease.”
From Identification of Candidate Signature Genes and Key Regulators Associated With Trypanotolerance in the Sheko Breed (2019) · cites this paper as Kaminski et al., 2001
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- Authors
- Kaminski, W. E., Lindahl, P., Lin, N. L., Broudy, V. C., Crosby, J. R., Hellström, M., Swolin, B., Bowen-Pope, D. F., Martin, P. J., Ross, R., Betsholtz, C., & Raines, E. W.
- Affiliations
- University of Washington (US)
- From the Departments of Pathology and Medicine, University of Washington School of Medicine; the Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA; the Department of Medical Biochemistry, University of Göteborg; and the Department of Clinical Chemistry, Sahlgrenska Hospital, Göteborg, Sweden.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2001-04-01
- Volume
- 97
- Issue
- 7
- Pages
- 1990-1998
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2116385071
- Cited by
- 77
- References
- 0
- Citations by year
- 2026: 1 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 1 · 2012: 6
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl055257-05)
- National Heart, Lung, and Blood Institute (HL-18645, HL03174, HL-55257, P01HL018645)
- National Cancer Institute (CA31615, R01CA031615)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- platelet-derived growth factor B, PDGF receptor beta, hematopoiesis, fetal liver cells, hematopoietic chimeras, embryonic lethality, cardiovascular defects, placental abnormalities, megakaryocytes, vascular endothelial cells, colony formation, metabolic stress
- MeSH terms
- Anemia, Animals, Blood Vessels, Erythroblastosis, Fetal, Female, Embryonic and Fetal Development, Fetal Diseases, Fetal Heart, Genes, Lethal, Genetic Complementation Test, Genotype, Hematopoiesis, Inflammation, Kidney, Liver, Male, Megakaryocytes, Placenta, Pregnancy, Radiation Chimera, Specific Pathogen-Free Organisms, Stress, Physiological, Bone Marrow Transplantation, Fetal Tissue Transplantation, Mice, Knockout, Hematopoietic Stem Cell Transplantation, Neovascularization, Physiologic, Proto-Oncogene Proteins c-sis, Receptor, Platelet-Derived Growth Factor beta, Mice
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