Details

Autor(en) / Beteiligte

• Merkulov, Sergei
• Zhang, Wan-Ming
• Komar, Anton A.
• Schmaier, Alvin H.
• Barnes, Ellen
• Zhou, Yihua
• Lu, Xincheng
• Iwaki, Takayuki
• Castellino, Francis J.
• Luo, Guangbin
• McCrae, Keith R.

Titel

Deletion of murine kininogen gene 1 (mKng1) causes loss of plasma kininogen and delays thrombosis

Ist Teil von

• Blood, 2008-02, Vol.111 (3), p.1274-1281

Ort / Verlag

Washington, DC: Elsevier Inc

Erscheinungsjahr

2008

Quelle

MEDLINE

Beschreibungen/Notizen

• High-molecular-weight kininogen (HK) plays an important role in the assembly of the plasma kallikrein-kinin system. While the human genome contains a single copy of the kininogen gene, 3 copies exist in the rat (1 encoding K-kininogen and 2 encoding T-kininogen). Here, we confirm that the mouse genome contains 2 homologous kininogen genes, mKng1 and mKng2, and demonstrate that these genes are expressed in a tissue-specific manner. To determine the roles of these genes in murine development and physiology, we disrupted mKng1, which is expressed primarily in the liver. mKng1−/− mice were viable, but lacked plasma HK and low-molecular-weight kininogen (LK), as well as ΔmHK-D5, a novel kininogen isoform that lacks kininogen domain 5. Moreover, despite normal tail vein bleeding times, mKng1−/− mice displayed a significantly prolonged time to carotid artery occlusion following Rose Bengal administration and laser-induced arterial injury. These results suggest that a single gene, mKng1, is responsible for production of plasma kininogen, and that plasma HK contributes to induced arterial thrombosis in mice.