ArticleBlood2008
Point mutation in the gene encoding p300 suppresses thrombocytopenia in Mpl-/- mice.
Article in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Cytokine pathway variants modulate platelet production: IFNA16 is a thrombocytosis susceptibility locus in humans.Blood advances · 2022Article
- Chromatin Dynamics in Intestinal Epithelial Homeostasis: A Paradigm of Cell Fate Determination versus Cell Plasticity.Stem cell reviews and reports · 2020Review
- A missense mutation in the MLKL brace region promotes lethal neonatal inflammation and hematopoietic dysfunction.Nature communications · 2020Article
- MYB controls erythroid versus megakaryocyte lineage fate decision through the miR-486-3p-mediated downregulation of MAF.Cell death and differentiation · 2015Article
- Protein lysine acetylation by p300/CBP.Chemical reviews · 2015Review
- The Myb-p300-CREB axis modulates intestine homeostasis, radiosensitivity and tumorigenesis.Cell death & disease · 2013Article
- Review
- Article
- A numerical analysis model for the interpretation of in vivo platelet consumption data.PloS one · 2013Article
- Article
- Cytopenia induction by 5-fluorouracil identifies thrombopoietic mutants in sensitized ENU mutagenesis screens.Experimental hematology · 2012Article
- Generation of N-ethyl-N-nitrosourea-induced mouse mutants with deviations in hematological parameters.Mammalian genome : official journal of the International Mammalian Genome Society · 2011Article
- Mouse models of diseases of megakaryocyte and platelet homeostasis.Mammalian genome : official journal of the International Mammalian Genome Society · 2011Review
- Integrated genome-wide chromatin occupancy and expression analyses identify key myeloid pro-differentiation transcription factors repressed by Myb.Nucleic acids research · 2011Article
- Random mutagenesis of the mouse genome: a strategy for discovering gene function and the molecular basis of disease.American journal of physiology. Gastrointestinal and liver physiology · 2011Review
- Regulation of hematopoietic stem cells by their mature progeny.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Target gene context influences the transcriptional requirement for the KAT3 family of CBP and p300 histone acetyltransferases.Epigenetics · 2010Review
- Mouse mutagenesis with the chemical supermutagen ENU.Methods in enzymology · 2010Article
- Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
In an N-nitroso-N-ethylurea (ENU) mutagenesis screen using Mpl(-/-) mice, we isolated a semidominant suppressor of thrombocytopenia, termed Plt6. The gene mutated in Plt6 mice encodes the transcriptional coregulator p300, and the mutation, a tyrosine to asparagine substitution at amino acid 630 (Y630N), disrupts the interaction between p300 and c-Myb. Mpl(-/-) p300(Plt6/+) mice displayed elevated platelet counts relative to Mpl(-/-) p300(+/+) controls, whereas mice homozygous for the Plt6 mutation produced supraphysiological levels of circulating platelets. On a wild-type genetic background, mice homozygous for the p300(Plt6) mutation, or recipients of Mpl(+/+) p300(Plt6/Plt6) bone marrow, also exhibited thrombocytosis as well as deficiencies in B-lymphoid cells. Increased platelet numbers in Plt6 mutant mice were accompanied by significant increases in megakaryocyte progenitor cells within the bone marrow and spleen with concomitantly elevated numbers of megakaryocytes. The expansion of megakaryocytopoiesis and suppression of Mpl(-/-) thrombocytopenia in Plt6 mutants is highly reminiscent of that observed in mice with mutations affecting the p300 partner protein c-Myb, suggesting an indispensable repressive role for the c-Myb/p300 transcriptional regulatory complex in megakaryocyte development, the inhibition of which allows substantial thrombopoietin (TPO)-independent platelet production.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.