Defective gamma-glutamyl carboxylase activity and bleeding in Rambouillet sheep

Area of Science:

• Veterinary Medicine
• Biochemistry
• Animal Genetics

Background:

• Increased lamb mortality in a Rambouillet sheep flock was linked to parturition complications.
• Affected neonates exhibited poor umbilical hemostasis, pale mucous membranes, and prolonged clotting times.

Purpose of the Study:

• To investigate the underlying cause of ineffective hemostasis and lamb mortality in the affected sheep flock.
• To characterize the coagulation defect and identify the specific molecular or enzymatic deficiency.

Main Methods:

• Coagulation assays including 1-stage prothrombin time and activated partial thromboplastin time were performed on affected lambs.
• Activity levels of hepatic enzymes, specifically gamma-glutamyl carboxylase and vitamin K(1) 2,3 epoxide reductase, were measured.
• The response to vitamin K(1) supplementation was assessed in affected lambs.

Main Results:

• Affected lambs showed prolonged prothrombin and partial thromboplastin times, indicating a coagulation cascade defect.
• Activity of vitamin K-dependent factors (II, VII, IX, X) was decreased, suggesting issues with gamma-glutamyl carboxylase or vitamin K(1) 2,3 epoxide reductase.
• Markedly decreased hepatic gamma-glutamyl carboxylase activity was confirmed in affected lambs, while vitamin K(1) 2,3 epoxide reductase activity was normal. Vitamin K(1) supplementation did not correct the deficiency.

Conclusions:

• The study confirms a hereditary defect in gamma-glutamyl carboxylase activity as the cause of impaired coagulation and lamb mortality in this flock.
• This flock of Rambouillet sheep serves as a valuable animal model for studying hereditary gamma-glutamyl carboxylase deficiency and its impact on hemostasis.