Canine Blood Disease Models and Stem Cell Resource

描述（由申请人提供）： 本研究资源申请（R24）的目的是为建立一个 犬血液病模型和干细胞（CBDSC）资源。犬血液病的目的 模型和干细胞资源是维持犬血友病A、血友病B、丙酮酸激酶 (PK)缺乏和循环造血（CH），为血液学研究提供实验动物， 提供犬血液、骨髓、外周血干细胞（PBSC）、造血祖细胞和 干细胞和技术专长与犬模型。这项研究资源补助金的目的是 是：（1）维持血友病，PK和CH犬的繁殖群体;（2）提供目的繁殖的实验 动物合作研究;和（3）提供犬血液和骨髓干细胞，组织 和犬验证的试剂，以及合格的研究者的测定。这些犬类模型 在主要研究者的实验室保存长达20年，并已用于协作 由NIH资助的研究人员在多个机构进行的研究，但尚未普遍提供。的 血友病B模型独特地倾向于产生抑制剂，使其成为基因治疗的理想选择， 耐受性研究PK缺陷犬在其他地方不可用，血友病A和CH犬 只有一个其他机构提供非常有限的数量。犬白细胞抗原（DLA）， 已经建立了繁殖群体和实验动物的组织相容性分型， 在移植研究中使用DLA相同、单倍性相同和不匹配的狗。狗是一口井 建立了用于骨髓移植、心脏和血友病研究的临床前模型。虽然 美国国立卫生研究院有大量的灵长类动物和啮齿类动物资源，目前还没有一个集中的犬类 资源，提供细胞，组织，试剂和专门的支持服务，作为研究资源， 研究人员使用犬模型。调查人员有超过30年的综合经验 与犬血液病研究，并唯一有资格建立犬血液病和干 细胞资源该项目将确保独特的犬血液病模型的生存， 由合格的研究人员访问模型，并建立犬血液的集中资源， 干细胞解决生物医学研究界未满足的需求。

DESCRIPTION (provided by applicant): The purpose of this research resource application (R24) is to provide support for the establishment of a canine blood disease models and stem cell (CBDSC) resource. The purpose of the canine blood disease models and stem cell resource is to maintain canine models of hemophilia A, hemophilia B, pyruvate kinase (PK) deficiency and cyclic hematopoiesis (CH), provide experimental animals for hematology research and to provide canine blood, bone marrow, peripheral blood stem cells (PBSCs), hematopoietic progenitor and stem cells and technical expertise with the canine model. The objectives of this research resource grant are: (1) maintain breeding colonies of hemophilia, PK and CH dogs; (2) provide purpose bred experimental animals for collaborative investigation; and (3) provide canine blood and bone marrow stem cells, tissues and canine-validated reagents, and assays to qualified investigators. The canine models have been maintained in the principal investigator's laboratory for up to 20 years and have been used in collaborative studies with NIH funded investigators at multiple institutions but have not been universally available. The hemophilia B model is uniquely prone to developing inhibitors making it ideal for gene therapy and tolerance studies. The PK deficient dogs are not available elsewhere and the hemophilia A and CH dogs are only available in very limited numbers at 1 other institution. Dog leukocyte antigen (DLA), histocompatability typing of the breeding colony and experimental animals has been established so that DLA identical, haploidentical and mismatched dogs are used in transplantation studies. The dog is a well established preclinical model for bone marrow transplantation, cardiac and hemophilia research. Although there are numerous NIH supported primate and rodent resources there presently is not a centralized canine resource to provide cells, tissues , reagents and specialized support services as a research resource for investigators using the canine model. The investigators have more than 30 years combined experience with canine blood disease research and are uniquely qualified to establish a canine blood disease and stem cell resource. This project will ensure the survival of unique canine blood disease models, provide broader access to the models by qualified investigators and establish a centralized resource for canine blood and stem cells to address unmet needs in biomedical research community.