Summary

Release of platelet dense granule contents occurs in responseto vascular injury, playing an important role in platelet aggregationand primary hemostasis. Abnormalities of the plateletdense granules results in a bleeding disorder of variable severitytermed "storage pool defect" (SPD). We have examined thefawn-hooded hypertensive (FHH) rat as a model of SPD inorder to genetically map the locus (Bd) responsible for prolongedbleeding. Platelet function assays of the FHH rat confirmedthe presence of a platelet dense granule SPD. Howeverelectron microscopy and lysosomal enzyme assays indicated differencesbetween the FHH rat and other rodent models of SPD. Genetic mapping through the use of congenic FHH ratslocalized the Bd locus to an approximately 1 cM region on ratchromosome 1. Through the use of comparative mappingbetween species and analysis of the initial draft of the ratgenome assembly, six known and thirty-four putative geneswere identified in the Bd locus. None of these genes have beenpreviously implicated in platelet function. Therefore positionalcloning of the gene responsible for the bleeding disorder in theFHH rat will lead to new insights in platelet physiology, withimplications for diagnosis and management of hemostatic andthrombotic disorders.