The KLKB1 gene provides instructions for creating prekallikrein, a protein primarily synthesized in the liver and found circulating in the blood. This protein is activated by Factor XII to form plasma kallikrein, a serine protease ^[1]. The function of this protein is critical for the intrinsic coagulation pathway (blood clotting) and the kallikrein-kinin system, which regulates blood pressure and inflammation ^[2]. The interaction of plasma kallikrein with Factor XII triggers a series of reactions that result in the release of bradykinin, a protein that promotes inflammation ^[3]. Mutations in the KLKB1 gene are associated with inherited conditions, most notably prekallikrein deficiency, which causes a prolonged activated partial thromboplastin time (a measure of blood clotting) but typically doesn't lead to clinical bleeding problems. More recently, mutations in the KLKB1 gene have also been linked to hereditary angioedema (HAE), a disorder characterized by episodes of severe swelling ^[4].

The B6-huKLKB1 mice are a humanized model constructed through gene editing technology, in which the mouse Klkb1 endogenous domain is replaced with the human KLKB1 domain. The murine signal peptide is kept. This model can be used for the study of the pathological mechanisms and treatment methods of prekallikrein deficiency and hereditary angioedema. It can also be applied to the development of KLKB1-targeted drugs.