Journal article
Point mutation in the gene encoding p300 suppresses thrombocytopenia in Mpl/mice
M Kauppi, JM Murphy, CA De Graaf, CD Hyland, KT Greig, D Metcalf, AA Hilton, NA Nicola, BT Kile, DJ Hilton, WS Alexander
Blood | Published : 2008
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-/- p300plt6/+ 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 p300Plt6 mutation, or recipients of Mpl+/+ p300 Plt6/Plt6 bone marrow, also exhibited ..
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Awarded by National Heart, Lung, and Blood Institute
Funding Acknowledgements
We thank Janelle Lochland, Jason Corbin, Sandra Mifsud, and Ladina DiRago for skilled technical assistance. This work was supported by a program grant (461219) and fellowships (D.J.H., J.M.M., W.S.A., N.A.N.) from the Australian National Health and Medical Research Council (Canberra, Australia), fellowships from the Australian Research Council (Canberra, Australia; B. T. K.) and Cancer Council of Victoria (Melbourne, Australia; D. M.), an RO1 grant from the National Heart, Lung, and Blood Institute (Bethesda, MD; HL080019) and a collaborative research grant from MuriGen (Melbourne, Australia).