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 insertin...

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Published in:PloS one 2014-02, Vol.9 (2), p.e88643
Main Authors: Azuma, Kotaro, Tsukui, Tohru, Ikeda, Kazuhiro, Shiba, Sachiko, Nakagawa, Kimie, Okano, Toshio, Urano, Tomohiko, Horie-Inoue, Kuniko, Ouchi, Yasuyoshi, Ikawa, Masahito, Inoue, Satoshi
Format: Article
Language:English
Subjects:
Alzheimer's disease
Alzheimers disease
Animals
Arthritis
Biology
Birth
Bleeding
Blood coagulation
Bone turnover
Carbon-Carbon Ligases - deficiency
Carbon-Carbon Ligases - metabolism
Cardiovascular disease
Coagulation
Gene Deletion
Gene expression
Geriatrics
Growth hormones
Hemorrhagic Disorders - enzymology
Hemorrhagic Disorders - pathology
Hepatocytes
Hepatocytes - enzymology
Hepatocytes - pathology
Integrases - metabolism
Kinases
Laboratories
Life span
Liver
Liver - enzymology
Liver - pathology
Longevity
Medicine
Metabolism
Mice
Mice, Knockout
Mutation
Organ Specificity
Proteins
Rodents
Signal transduction
Systematic review
Thrombosis
Vitamin K
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0088643