Genetic mapping and characterization of the bleeding disorder in the fawn-hooded hypertensive rat

Yvonne H. Datta; Francisca C.Wu; Pierre C. Dumas; Artur Rangel-Filho; Milton W. Datta; Gang Ning; Brian C. Cooley; Rebecca R. Majewski; Abraham P. Provoost; Howard J. Jacob

doi:10.1055/s-0037-1613405

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2003; 89(06): 1031-1042
DOI: 10.1055/s-0037-1613405

Platelets and Blood Cells

Schattauer GmbH

Genetic mapping and characterization of the bleeding disorder in the fawn-hooded hypertensive rat

Authors

Yvonne H. Datta

¹The Medical College of Wisconsin, Milwaukee, Wisconsin, USA

²Blood Research Institute, Milwaukee, Wisconsin, USA
Francisca C.Wu

¹The Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Pierre C. Dumas

¹The Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Artur Rangel-Filho

¹The Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Milton W. Datta

¹The Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Gang Ning

¹The Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Brian C. Cooley

¹The Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Rebecca R. Majewski

¹The Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Abraham P. Provoost

³Erasmus University, Rotterdam, The Netherlands
Howard J. Jacob

¹The Medical College of Wisconsin, Milwaukee, Wisconsin, USA

Abstract

Summary

Release of platelet dense granule contents occurs in response to vascular injury, playing an important role in platelet aggregation and primary hemostasis. Abnormalities of the platelet dense granules results in a bleeding disorder of variable severity termed “storage pool defect” (SPD). We have examined the fawn-hooded hypertensive (FHH) rat as a model of SPD in order to genetically map the locus (Bd) responsible for prolonged bleeding. Platelet function assays of the FHH rat confirmed the presence of a platelet dense granule SPD. However electron microscopy and lysosomal enzyme assays indicated differences between the FHH rat and other rodent models of SPD. Genetic mapping through the use of congenic FHH rats localized the Bd locus to an approximately 1 cM region on rat chromosome 1. Through the use of comparative mapping between species and analysis of the initial draft of the rat genome assembly, six known and thirty-four putative genes were identified in the Bd locus. None of these genes have been previously implicated in platelet function. Therefore positional cloning of the gene responsible for the bleeding disorder in the FHH rat will lead to new insights in platelet physiology, with implications for diagnosis and management of hemostatic and thrombotic disorders.

Keywords

Platelets - dense granules - storage pool defect - rats - genetic mapping

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Referenzen

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