title: Liver-specific γ-glutamyl carboxylase-deficient mice display bleeding diathesis and short life span.
abstract: Vitamin K is a fat-soluble vitamin that plays important roles in blood coagulation and bone metabolism. One of its functions is as a co-factor for γ-glutamyl carboxylase (Ggcx). Conventional knockout of Ggcx causes death shortly after birth in homozygous mice. We created Ggcx-floxed mice by inserting loxP sequences at the sites flanking exon 6 of Ggcx. By mating these mice with albumin-Cre mice, we generated Ggcx-deficient mice specifically in hepatocytes (Ggcx(Δliver/Δliver) mice). In contrast to conventional Ggcx knockout mice, Ggcx(Δliver/Δliver) mice had very low activity of Ggcx in the liver and survived several weeks after birth. Furthermore, compared with heterozygous mice (Ggcx(+/Δliver) ), Ggcx(Δliver/Δliver) mice had shorter life spans. Ggcx(Δliver/Δliver) mice displayed bleeding diathesis, which was accompanied by decreased activity of coagulation factors II and IX. Ggcx-floxed mice can prove useful in examining Ggcx functions in vivo.
authors: Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors: Kotaro
authors: K
authors: Azuma
authors: Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama, Japan.
authors: Tohru
authors: T
authors: Tsukui
authors: Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama, Japan.
authors: Kazuhiro
authors: K
authors: Ikeda
authors: Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama, Japan.
authors: Sachiko
authors: S
authors: Shiba
authors: Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe, Hyogo, Japan.
authors: Kimie
authors: K
authors: Nakagawa
authors: Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe, Hyogo, Japan.
authors: Toshio
authors: T
authors: Okano
authors: Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors: Tomohiko
authors: T
authors: Urano
authors: Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama, Japan.
authors: Kuniko
authors: K
authors: Horie-Inoue
authors: Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors: Yasuyoshi
authors: Y
authors: Ouchi
authors: Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
authors: Masahito
authors: M
authors: Ikawa
authors: Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan ; Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama, Japan ; Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors: Satoshi
authors: S
authors: Inoue
mesh_terms: D000818:Animals; D019735:Carbon-Carbon Ligases / Q000172:deficiency* / Q000378:metabolism; D017353:Gene Deletion; D006474:Hemorrhagic Disorders / Q000201:enzymology* / Q000473:pathology*; D022781:Hepatocytes / Q000201:enzymology / Q000473:pathology; D019426:Integrases / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008136:Longevity; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity
chemical_list: C045073:Cre recombinase; D019426:Integrases; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase