Liver-Specific γ-Glutamyl Carboxylase-Deficient Mice Display Bleeding Diathesis and Short Life Span
Liver-Specific γ-Glutamyl Carboxylase-Deficient Mice Display Bleeding Diathesis and Short Life Span
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.
- University of Tokyo Japan
- Saitama Medical University Japan
- Kobe Pharmaceutical University Japan
- Osaka University Japan
Mice, Knockout, 570, Integrases, Science, Q, Longevity, R, 610, Hemorrhagic Disorders, Mice, Carbon-Carbon Ligases, Liver, Organ Specificity, Hepatocytes, Medicine, Animals, Gene Deletion, Research Article
Mice, Knockout, 570, Integrases, Science, Q, Longevity, R, 610, Hemorrhagic Disorders, Mice, Carbon-Carbon Ligases, Liver, Organ Specificity, Hepatocytes, Medicine, Animals, Gene Deletion, Research Article
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