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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5270-5275. Prepublished online as a Blood First Edition Paper on February 27, 2007; DOI 10.1182/blood-2006-12-064188. This Article Full Text (PDF) All Versions of this Article: blood-2006-12-064188v1 109/12/5270    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zhu, A. Articles by Ginsburg, D. Search for Related Content PubMed PubMed Citation Articles by Zhu, A. Articles by Ginsburg, D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 26, 2006 Accepted February 21, 2007 Fatal hemorrhage in mice lacking -glutamyl carboxylase Aihua Zhu, Hongmin Sun, Richard M. Raymond Jr., Barbara C. Furie, Bruce Furie, Mila Bronstein, Randal J Kaufman, Randal Westrick, and David Ginsburg* Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI, United States Life Sciences Institute, University of Michigan, Ann Arbor, MI, United States Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States Departments of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, MI, United States Department of Human Genetics, University of Michigan, Ann Arbor, MI, United States * Corresponding author; email: ginsburg{at}umich.edu. The carboxylation of glutamic acid residues to -carboxyglutamic acid (Gla) by the vitamin K-dependent -glutamyl carboxylase (-carboxylase) is an essential post-translational 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 -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 mid-embryonic 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 -carboxylation, at least in the developing embryo and neonate, are primarily restricted to components of the blood coagulation cascade. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. C McCann and B. N Ames Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging? Am. J. Clinical Nutrition, October 1, 2009; 90(4): 889 - 907. [Abstract] [Full Text] [PDF] Q. Li, L. J. Schurgers, A. C.M. Smith, M. Tsokos, J. Uitto, and E. W. Cowen Co-Existent Pseudoxanthoma Elasticum and Vitamin K-Dependent Coagulation Factor Deficiency: Compound Heterozygosity for Mutations in the GGCX Gene Am. J. Pathol., February 1, 2009; 174(2): 534 - 540. [Abstract] [Full Text] [PDF]

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