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 犬血液病模型与干细胞(CBDSC)资源犬血液病的目的 模型和干细胞来源是维持犬的血友病A、血友病B、丙酮酸激酶模型 (PK)缺乏和周期性造血(CH)，为血液学研究提供实验动物和 提供犬血、骨髓、外周血干细胞、造血祖细胞和 干细胞和犬类模型的技术专长。这项研究资源拨款的目标是 是：(1)维持血友病、PK和CH犬的繁育群体；(2)提供有目的的饲养实验 用于协作研究的动物；以及(3)提供犬血和骨髓干细胞、组织 和犬类验证试剂，以及合格调查人员的化验。犬类模型已经被 在首席调查员的实验室中维护长达20年，并已用于协作 与NIH资助的研究人员在多个机构进行了研究，但尚未普遍获得。这个 血友病B模型特别容易开发抑制剂，使其成为基因治疗和 耐受性研究。其他地方没有PK缺陷的狗，血友病A和CH狗 仅在其他一家机构提供非常有限的数量。犬白细胞抗原(DLA)， 建立了繁殖群体和实验动物的组织相容性分型 DLA相合、半相合和不相合的狗被用于移植研究。这只狗是一口井 建立了骨髓移植、心脏和血友病研究的临床前模型。虽然 有许多NIH支持的灵长类和啮齿动物资源，目前还没有一只集中的犬科动物 提供细胞、组织、试剂和专业支持服务的资源，作为 研究人员使用的是犬类模型。调查人员有30多年的综合经验 具有犬血液病研究和独家资质，可建立犬血液病和犬只干 蜂窝资源。该项目将确保犬独特的血液病模型存活，提供更广阔的应用前景 由合格的研究人员访问模型，并建立一个集中的犬血和 干细胞以解决生物医学研究界未得到满足的需求。

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.