| First Author | Zhu A | Year | 2007 |
| Journal | Blood | Volume | 109 |
| Issue | 12 | Pages | 5270-5 |
| PubMed ID | 17327402 | Mgi Jnum | J:120784 |
| Mgi Id | MGI:3707985 | Doi | 10.1182/blood-2006-12-064188 |
| Citation | Zhu A, et al. (2007) Fatal hemorrhage in mice lacking gamma-glutamyl carboxylase. Blood 109(12):5270-5 |
| abstractText | 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. |
