The animal core will breed transgenic mice which will be identified and characterized for use in Project 1:Design of alpha-chains that fully neutralize polymerization; Project 2: MRl and NIRS in SS patients and mice; Project 3: Sickle Cell Adhesion; and Project 4: Sickle vasocclusion: pleiotropism, epistasis, epigenetics. Our function will be mainly to provide assistance to investigators in the marking, identification, and record keeping of founders and their offspring. These mice will include the NY1KO mice that express exclusively human hemoglobins: HbS and three different levels of HbF; the BERK mice (originally described by Paszty et al) and BERK mice expressing HbF. Knockouts for iNOS, nNOS, vWF, and P-selectin will be bred into our sickle lines as will a variety of knockout and transgenic lines described in Project 4. Also included are mice that express exclusively HbC and exclusively HbA, as well as suitable control mice for all of the proposed experiments. This core also provides analytic services for other projects: protein identification and quantitation (HPLC, IEF, mass spec), red cell characterization (p50, intracellular polymerization, 2,3-DPG analysis), and red cell density distribution.
|Chen, Qiuying; Fabry, Mary E; Rybicki, Anne C et al. (2012) A transgenic mouse model expressing exclusively human hemoglobin E: indications of a mild oxidative stress. Blood Cells Mol Dis 48:91-101|
|Srinivasulu, Sonati; Acharya, A Seetharama; Prabhakaran, Muthuchidambaran et al. (2007) HbS-Savaria: the anti-polymerization effect of a single mutation in human alpha-chains. Protein J 26:523-32|
|Finnegan, Eileen M; Turhan, Aslihan; Golan, David E et al. (2007) Adherent leukocytes capture sickle erythrocytes in an in vitro flow model of vaso-occlusion. Am J Hematol 82:266-75|
|Chen, Qiuying; Lalezari, Iraj; Nagel, Ronald L et al. (2005) Liganded hemoglobin structural perturbations by the allosteric effector L35. Biophys J 88:2057-67|
|Chen, Qiuying; Vekilov, Peter G; Nagel, Ronald L et al. (2004) Liquid-liquid phase separation in hemoglobins: distinct aggregation mechanisms of the beta6 mutants. Biophys J 86:1702-12|
|Chen, Qiuying; Bouhassira, Eric E; Besse, Arnaud et al. (2004) Generation of transgenic mice expressing human hemoglobin E. Blood Cells Mol Dis 33:303-7|