Journal article
Thrombocytopenia and erythrocytosis in mice with a mutation in the gene encoding the hemoglobin β minor chain
M Kauppi, AA Hilton, D Metcalf, AP Ng, CD Hyland, JE Collinge, BT Kile, DJ Hilton, WS Alexander
Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2012
Abstract
Diverse mutations in the genes encoding hemoglobin (Hb) have been characterized in human disease. We describe here a mutation in the mouse Hbb-b2 gene, denoted Plt12, that precisely mimics the human hemoglobin Hotel Dieu variant. The mutation results in increased affinity of Hb for oxygen and Plt12 mutant mice exhibited reduced partial pressure of O2 in the blood, accompanied by erythrocytosis characterized by elevated erythropoietin levels and splenomegaly with excess erythropoiesis. Most homozygous Hbb-b2 Plt12/Plt12 mice succumbed to early lethality associated with emphysema, cardiac abnormalities, and liver degeneration. Survivors displayed a marked thrombocytopenia without significant d..
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Awarded by Australian National Health and Medical Research Council
Funding Acknowledgements
We thank Michael O'Mahoney, Patricia Servadei, and Ray Czajko for blood gas and chromatographic analysis; Sarah Siggins for assistance with immunohistochemistry; Kelly Trueman, Emma Lamera, Laura Wilkins, and Shauna Ross for excellent animal husbandry; and Jason Corbin, Katya Henley, and Janelle Lochland for excellent technical assistance. This work was supported by Program Grant 461219, fellowships (to W. S. A. and B. T. K.), and Independent Research Institutes Infrastructure Support Scheme Grant 361646 from the Australian National Health and Medical Research Council; the Australian Research Council (B. T. K.); the Carden Fellowship Fund (D. M.) of the Cancer Council, Victoria; a Haematology Society of Australia & New Zealand (HSANZ)/AMGEN New Investigator Scholarship (to A.P.N.); the Australian Cancer Research Fund; a Victorian State Government Operational Infrastructure Support grant; and Murigen Pty Ltd.