Fatal hemorrhage in mice lacking gamma-glutamyl carboxylase.

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Zhu A, Sun H, Raymond RM Jr, Furie BC, Furie B, Bronstein M, Kaufman RJ, Westrick R, Ginsburg D

Fatal hemorrhage in mice lacking gamma-glutamyl carboxylase.

Blood. 2007 Jun 15;109(12):5270-5. Epub 2007 Feb 27.

PubMed ID

17327402 [ View in PubMed

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Abstract

The carboxylation of glutamic acid residues to gamma-carboxyglutamic acid (Gla) by the vitamin K-dependent gamma-glutamyl carboxylase (gamma-carboxylase) is an essential posttranslational modification required for the biological activity of a number of proteins, including proteins involved in blood coagulation and its regulation. Heterozygous mice carrying a null mutation at the gamma-carboxylase (Ggcx) gene exhibit normal development and survival with no evidence of hemorrhage and normal functional activity of the vitamin K-dependent clotting factors IX, X, and prothrombin. Analysis of a Ggcx(+/-) intercross revealed a partial developmental block with only 50% of expected Ggcx(-/-) offspring surviving to term, with the latter animals dying uniformly at birth of massive intra-abdominal hemorrhage. This phenotype closely resembles the partial midembryonic loss and postnatal hemorrhage previously reported for both prothrombin- and factor V (F5)-deficient mice. These data exclude the existence of a redundant carboxylase pathway and suggest that functionally critical substrates for gamma-carboxylation, at least in the developing embryo and neonate, are primarily restricted to components of the blood coagulation cascade.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Glutamic acid	Vitamin K-dependent gamma-carboxylase	Protein	Humans	Unknown	Not Available	Details