Core--Transgenic Mice

动物核心将培育转基因小鼠，用于项目1：设计完全中和聚合的阿尔法链；项目2：SS患者和小鼠的MRL和NIRS；项目3：镰状细胞黏附；以及项目4：镰状血管闭塞：多向性、上位性、表观遗传学。我们的职能将主要是协助调查人员对创始人及其后代进行标记、身份识别和记录保存。这些小鼠将包括只表达人类血红蛋白的NY1KO小鼠：HBS 和三种不同水平的HBF；Berk小鼠(最初由Paszty等人描述)和表达HBF的Berk小鼠。INOS、nNOS、vWF和P-选择素的敲除将培育成我们的镰刀系，以及项目4中描述的各种敲除和转基因系。还包括只表达HBC和HBA的小鼠，以及适用于所有拟议实验的对照小鼠。该核心还为其他项目提供分析服务：蛋白质鉴定和定量(高效液相、离子交换、质谱仪)、红细胞特性(p50、细胞内聚合、2，3-DPG分析)和红细胞密度分布。

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.