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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by He, Z. Articles by Russell, J. E. Search for Related Content PubMed PubMed Citation Articles by He, Z. Articles by Russell, J. E. Related Collections Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 February 2001, Vol. 97, No. 4, pp. 1099-1105 RED CELLS Expression, purification, and characterization of human hemoglobins Gower-1 (22), Gower-2 (22), and Portland-2 (22) assembled in complex transgenic-knockout mice Zhenning He and J. Eric Russell From the Departments of Medicine and Pediatrics, University of Pennsylvania School of Medicine and The Children's Hospital of Philadelphia, Philadelphia, PA. Embryonic - and -globin subunits assemble with each other and with adult - and -globin subunits into hemoglobin heterotetramers in both primitive and definitive erythrocytes. The properties of these hemoglobinsHbs Gower-1 (22), Gower-2 (22), and Portland-2 (22)have been incompletely described as they are difficult to obtain in quantity from either primary human tissue or conventional expression systems. The generation of complex transgenic-knockout mice that express these hemoglobins at levels between 24% and 70% is described, as are efficient methods for their purification from mouse hemolysates. Key physiological characteristicsincluding P50, Hill coefficient, Bohr effect, and affinity for 2,3-BPGwere established for each of the 3 human hemoglobins. The stability of each hemoglobin in the face of mechanical, thermal, and chemical stresses was also determined. Analyses indicate that the -for- exchange distinguishing Hb Portland-2 and Hb A alters hemoglobin O2-transport capacity by increasing its P50 and decreasing its Bohr effect. By comparison, the -for- exchange distinguishing Hb Gower-2 and Hb A has little impact on these same functional parameters. Hb Gower-1, assembled entirely from embryonic subunits, displays an elevated P50 level, a reduced Bohr effect, and increased 2,3-BPG binding compared to Hb A. The data support the hypothesis that Hb Gower-2, assembled from reactivated  globin in individuals with defined hemoglobinopathies and thalassemias, would serve as a physiologically acceptable substitute for deficient or dysfunctional Hb A. In addition, the unexpected properties of Hb Gower-1 call into question a common hypothesis for its primary role in embryonic development. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Z. He and J. E. Russell Dynamic posttranscriptional regulation of {epsilon}-globin gene expression in vivo Blood, January 15, 2007; 109(2): 795 - 801. [Abstract] [Full Text] [PDF] Z. He and J. E. Russell A human embryonic hemoglobin inhibits Hb S polymerization in vitro and restores a normal phenotype to mouse models of sickle cell disease PNAS, August 6, 2002; 99(16): 10635 - 10640. [Abstract] [Full Text] [PDF]

	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020