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: Kotaro Azuma, Tohru Tsukui, Kazuhiro Ikeda, Sachiko Shiba, Kimie Nakagawa, Toshio Okano, Tomohiko Urano, Kuniko Horie-Inoue, Yasuyoshi Ouchi, Masahito Ikawa, Satoshi Inoue
• Journal: PloS one (PLoS One) Vol. 9 Issue 2 Pg. e88643 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24520408 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cre recombinase
• Integrases
• Carbon-Carbon Ligases
• glutamyl carboxylase

Topics

• Animals
• Carbon-Carbon Ligases (deficiency, metabolism)
• Gene Deletion
• Hemorrhagic Disorders (enzymology, pathology)
• Hepatocytes (enzymology, pathology)
• Integrases (metabolism)
• Liver (enzymology, pathology)
• Longevity
• Mice
• Mice, Knockout
• Organ Specificity