Journal
BLOOD
Volume 111, Issue 3, Pages 1274-1281Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2007-06-092338
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Categories
Funding
- NHLBI NIH HHS [R01 HL052779, R01 HL076810, HL052779, HL073750, P01 HL073750, R01 HL089796, HL076810] Funding Source: Medline
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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 Delta mHK-D5, a novel kininogen isoform that lacks kininogen domain 5. Moreover, despite normal tall 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.
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