title: Defective gamma-glutamyl carboxylase activity and bleeding in Rambouillet sheep.
abstract: A flock of Rambouillet sheep was examined because of increased lamb mortality caused by ineffective hemostasis at parturition. Neonatal-affected lambs presented with inadequate hemostasis at the umbilicus, pale mucus membranes, and markedly prolonged activated clotting time. Affected lambs had consistently prolonged 1-stage prothrombin times and activated partial thromboplastin times that supported a defect in the common pathway or defects in both the intrinsic and extrinsic pathway of the coagulation cascade. Decreased activity of vitamin K-dependent procoagulant factors II, VII, IX, and X in male and female lambs suggested either a defect of the hepatic enzyme gamma-glutamyl carboxylase, or vitamin K(1) 2,3 epoxide reductase. Affected lamb hepatic gamma-glutamyl carboxylase activity was markedly decreased compared with that of age- and sex-matched control lambs, while vitamin K(1) 2,3 epoxide reductase and glucose-6-phosphatase activities were similar between an affected and normal lamb. Subcutaneous vitamin K(1) supplementation did not increase vitamin K-dependent procoagulant factor activities in 3 lambs administered vitamin K(1) daily. These data confirm defective gamma-glutamyl carboxylase activity as the cause of impaired coagulation of sheep in this flock. This flock represents the only viable animal model of hereditarily defective gamma-glutamyl carboxylase activity.
authors.affiliation: Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA. jeremy-johnson@idexx.com
authors.forename: J S
authors.initials: JS
authors.lastname: Johnson
authors.forename: B A
authors.initials: BA
authors.lastname: Soute
authors.forename: C S
authors.initials: CS
authors.lastname: Olver
authors.forename: D C
authors.initials: DC
authors.lastname: Baker
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D025861:Blood Coagulation Disorders, Inherited / Q000201:enzymology / Q000662:veterinary*; D001779:Blood Coagulation Factors / Q000378:metabolism; D019735:Carbon-Carbon Ligases / Q000378:metabolism*; D005260:Female; D006487:Hemostasis; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D012756:Sheep / Q000145:classification; D012757:Sheep Diseases / Q000201:enzymology*; D013997:Time Factors
chemical_list: D001779:Blood Coagulation Factors; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase