The purpose of this resource grant is to function as a core to maintain and create dogs with hemophilia A, hemophilia B, and von Willebrand disease (WVD) for collaborations with other investigators. Our objectives 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, affordable research animals with these bleeding disorders in a cost effective manner;and 3) To provide specialized support services for research projects using these dogs including canine blood banking and coagulation analyses. These dogs, identified by Dr. Kenneth M. Brinkhous, model human hemophilias and VWD and have been maintained for >50 years at UNC largely through NIH support. Research using the FOBRL dogs has more than doubled during the past 20 years and 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. Thus many advisory boards recommend these dogs as essential for preclinical testing of new treatments for the hemophilias, VWD, and hemorrhage. Major accomplishments during the past 5 years include 24 peer-reviewed publications, over 36 abstract presentations, and obtaining funding separate from but leveraged by this grant that built new, dedicated hemophilia and VWD dog housing. 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. Current research addresses several unmet national needs that include testing new treatments for bleeding, developing a new strain of hemophilia A dogs with inhibitors, and determining the acute and chronic sequelae of gene therapy on genetic diseases. 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 and the survival of this colony would be jeopardized. The cost of establishing a colony at each investigator's institution is prohibitive. This Resource Grant is essential to ensure the survival of the colony in an established, successful environment.
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