biostudies-literatureMerkulov SNHLBI NIH HHS1274-81https://www.ebi.ac.uk/biostudies/studies/S-EPMC2214772biostudies-literatureUnknown111(3)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 DeltamHK-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.BloodDeletion of murine kininogen gene 1 (mKng1) causes loss of plasma kininogen and delays thrombosis.PMC2214772R01 HL052779R01 HL076810HL052779HL076810P01 HL073750R01 HL089796HL073750Komar AALu XIwaki TMerkulov SMcCrae KRLuo GSchmaier AHCastellino FJZhou YBarnes EZhang WMfalseDeletion of murine kininogen gene 1 (mKng1) causes loss of plasma kininogen and delays thrombosis.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 DeltamHK-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.2008-01-01T00:00:00Z2008 Feb2024-11-15T17:53:30.592Z2019-03-27T02:43:51ZS-EPMC22147721800016810.1182/blood-2007-06-092338