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- Title
Liver-Specific γ-Glutamyl Carboxylase-Deficient Mice Display Bleeding Diathesis and Short Life Span.
- Authors
Azuma, Kotaro; Tsukui, Tohru; Ikeda, Kazuhiro; Shiba, Sachiko; Nakagawa, Kimie; Okano, Toshio; Urano, Tomohiko; Horie-Inoue, Kuniko; Ouchi, Yasuyoshi; Ikawa, Masahito; Inoue, Satoshi
- 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 (GgcxΔliver/Δliver mice). In contrast to conventional Ggcx knockout mice, GgcxΔliver/Δliver mice had very low activity of Ggcx in the liver and survived several weeks after birth. Furthermore, compared with heterozygous mice (Ggcx+/Δliver), GgcxΔliver/Δliver mice had shorter life spans. GgcxΔliver/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.
- Subjects
CARBOXYLASES; HEMORRHAGE; DISEASE susceptibility; LIFE spans; VITAMIN K; BLOOD coagulation; BONE metabolism
- Publication
PLoS ONE, 2014, Vol 9, Issue 2, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0088643