DESCRIPTION (provided by applicant): This purpose of this resource grant is to function as a core to maintain and create dogs with hemophilia A and B and von Willebrand disease (vWD) for collaborations with other investigators. In the first 3 years of funding, collaborations with at least 12 teams of investigators have been reported in 12 manuscripts. The research is funded on 18 separate research grants. Our objectives in this Resource Grant are: 1) To maintain a breeding colony of well-characterized dogs with genetically-determined bleeding disorders at the Francis Owen Blood Research Laboratory (FOBRL), University of North Carolina, Chapel Hill; 2) To produce purpose-bred research animals with these bleeding disorders; and 3) To provide specialized support services for research projects using these dogs including canine blood banking and coagulation analyses. These dogs modeling human hemophilia A, hemophilia B, and vWD were identified by Dr. Kenneth M. Brinkhous and have been maintained for >50 years in Chapel Hill largely through NIH support. A highly trained staff at the FOBRL has several years of experience in maintaining these special dogs with a dedicated canine blood bank, developing canine coagulation assays, conducting investigations, and collaborating successfully with investigators worldwide. Research using the FOBRL dogs has led to discoveries that have revolutionized the treatment, of inherited and acquired bleeding and thrombotic disorders. Many therapeutic agents were developed and tested in these dogs and successfully translated into clinical therapeutics. Current research with these dogs addresses several unmet national needs including developing new treatments for bleeding, and determining the acute and chronic sequelae of gene therapy on genetic diseases. These dogs constitute an important national resource and are recommended by many investigators and advisory boards as essential for pre-clinical testing of new treatments for the hemophilias, vWD, and hemorrhage. The use of these hemophilic dogs has more than doubled during the past two decades. This grant is the only support for maintenance of this colony. Without this grant, new research using these valuable bleeder dogs would be very difficult and expensive to initiate. The survival of the FOBRL colony would be jeopardized. The cost of establishing a colony at each investigator's institution is prohibitive. The primary benefit of this grant will be to maintain breeding stock for producing affordable, purpose-bred research animals in a cost-effective manner for the research community. This Resource Grant is essential to ensure the survival of the colony in an established, successful environment.