? 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. ? ? ? ?