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.