NDLI: Thrombocytopenia and erythrocytosis in mice with a mutation in the gene encoding the hemoglobin β minor chain

Content Provider	PubMed Central
Author	Kauppi, Maria Hilton, Adrienne A. Metcalf, Donald Ng, Ashley P. Hyland, Craig D. Collinge, Janelle E. Kile, Benjamin T. Hilton, Douglas J. Alexander, Warren S.
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-b2Plt12/Plt12 mice succumbed to early lethality associated with emphysema, cardiac abnormalities, and liver degeneration. Survivors displayed a marked thrombocytopenia without significant deficiencies in the numbers of megakaryocytes or megakaryocyte progenitor cells. The lifespan of platelets in the circulation of Hbb-b2Plt12/Plt12 mice was normal, and splenectomy did not correct the thrombocytopenia, suggesting that increased sequestration was unlikely to be a major contributor. These data, together with the observation that megakaryocytes in Hbb-b2Plt12/Plt12 mice appeared smaller and deficient in cytoplasm, support a model in which hypoxia causes thrombocytopenia as a consequence of an inability of megakaryocytes, once formed, to properly mature and produce sufficient platelets. The Plt12 mouse is a model of high O2-affinity hemoglobinopathy and provides insights into hematopoiesis under conditions of chronic hypoxia.
Related Links	http://dx.doi.org/10.1073/pnas.1119146109
Ending Page	581
Page Count	6
Starting Page	576
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	2
Volume Number	109
Language	English
Publisher	National Academy of Sciences
Publisher Date	2012-01-10
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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