| First Author | Spohn G | Year | 2009 |
| Journal | Thromb Haemost | Volume | 101 |
| Issue | 6 | Pages | 1044-50 |
| PubMed ID | 19492146 | Mgi Jnum | J:207884 |
| Mgi Id | MGI:5559848 | Doi | 10.1160/TH09-03-0204 |
| Citation | Spohn G, et al. (2009) VKORC1 deficiency in mice causes early postnatal lethality due to severe bleeding. Thromb Haemost 101(6):1044-50 |
| abstractText | Vitamin K hydroquinone is oxidised to the epoxide form (K>O) during vitamin K-dependent posttranslational gamma-glutamyl carboxylation resulting in biological active so called vitamin K-dependent proteins. In turn, K>O is reduced by the enzyme VKORC1 (vitamin K epoxide reductase complex component 1) to complete the vitamin K cycle. To investigate the biological role of VKORC1 in vivo, we generated VKORC1 knockout mice. Homozygous VKORC1-deficient mice developed normally until birth. Within 2-20 days after birth, the knockout mice died due to extensive, predominantly intracerebral haemorrhage. Bleeding resulted from a severe deficiency of gamma-carboxylated clotting factors. This lethal phenotype could be rescued by oral administration of vitamin K. Additionally, morphometric analysis of the limbs in VKORC1-deficient animals revealed reduced length of bone calcification relative to wild-type control mice. The observed phenotype of VKORC1 knockout mice excludes the existence of other enzymes with VKOR activity that can substitute to supply vitamin K hydroquinone required for maturation of blood clotting factors. Thus, our study underscores the essential role of VKORC1 in vitamin K-dependent gamma-glutamyl carboxylation. |
