Colonies of animals with inherited coagulation and platelet function defects are maintained for genetic, biochemical and physiological studies; production of reagents for coagulation tests; and evaluation of hemostasis. These include dogs with hemophilia A, hemophilia B, von Willebrand's disease (VWD), factor VII deficiency, warfarin hypersensitivity, thrombasthenic thrombopathia, thrombopathia and various combinations of these defects,; fawn-hooded rats with platelet storage pool disease, spontaneous glomerulosclerosis and hypertension; and Syrian hamsters with age-associated spontaneous atrial thrombosis. Studies with these naturally occurring animal models examine basic mechanisms of hemostasis and thrombosis in comparison to analogous human diseases. The objectives for the next period include continuing to diagnose, characterize, maintain and research animal models of spontaneous hemorrhagic and thrombotic diseases; studies by in vitro and in vivo methods of factor VIII in normal, hemophilic and VWD dogs; studies of the platelet function defect of basset hounds; collaboration with other investigators in research projects; provision of reagents, genetic material and other animal products based on their availability; consultation about the comparative aspects of hemostasis research and bleeding disorders; ad provision of space for visiting scientists or laboratory personnel.
Specific aims for the period include: refinement of a multimeric assay for canine von Willebrand's factor (VWF) for diagnostic and biochemical studies; research with rDNA-derived human factor VIII in hemophilic and VWD dogs; studies of the molecular and functional properties of canine VWF and factor VIII coagulant in thyroid disease; and platelet studies focused on definition of the biochemical defect of canine thrombopathia, specifically its abnormal signal-response coupling via the cyclic nucleotide, phosphodiesterase and calmodulin pathways. Screening tests for thrombopathia using whole blood and platelet agonists and the snake-venom-induced agglutination assay for canine plasma VWF are used in the field for diagnostic purposes.
| Chow, Andrew; Brown, Brian D; Merad, Miriam (2011) Studying the mononuclear phagocyte system in the molecular age. Nat Rev Immunol 11:788-98 |
