huF9 Mouse

Hemophilia is a group of inherited bleeding disorders primarily caused by deficiency or dysfunction of coagulation factor VIII or IX, leading to impaired coagulation. Patients typically present with prolonged clotting time, easy bleeding even after minor trauma, and in severe cases, spontaneous bleeding, commonly occurring in joints and deep tissues. Hemophilia is mainly classified into three types: type A (factor VIII deficiency), type B (factor IX deficiency), and type C (factor XI deficiency). Among these, types A and B are the most prevalent. Hemophilia A is caused by mutations in the F8 gene, resulting in factor VIII deficiency, while hemophilia B is caused by mutations in the F9 gene, leading to factor IX deficiency ^[1]. Coagulation factor IX, encoded by the F9 gene, is activated to FIXa during coagulation and works in concert with FVIIIa, Ca2+, and membrane phospholipids to activate factor X. Hemophilia A and B are both X-linked recessive genetic disorders with a higher incidence in males. The incidence of hemophilia B is approximately 1/25,000 to 1/30,000, accounting for about 15%-20% of all hemophilia cases ^[2].

Currently, coagulation factor replacement therapy is the primary treatment for hemophilia ^[2]. For hemophilia A, the treatment is intravenous injection of factor VIII concentrates; for hemophilia B, factor IX concentrates are injected to maintain normal levels of coagulation factors in patients. However, this therapy is a supplementary approach, requiring lifelong regular injections, which may not only cause side effects but also impose a substantial economic burden on patients. Therefore, gene therapy, particularly for hemophilia B, is considered a highly promising research direction. Etranacogene dezaparvovec (brand name Hemgenix) is the first gene therapy for hemophilia B approved by the U.S. FDA ^[3-4]. This therapy utilizes adeno-associated virus vector AAV5 to deliver the coagulation factor IX gene to patient hepatocytes, thereby increasing FIX activity in vivo and reducing bleeding events ^[3]. Gene therapy is considered a potential curative approach for hemophilia B. Considering the genetic differences between animals and humans, and that most gene therapies target human genes, humanizing mouse genes will help accelerate the drug pipeline of gene therapies into the clinical stage.

This strain is a humanized mouse F9 gene model, which can be used for preclinical evaluation of hemophilia B pathogenesis and therapeutic drugs. Homozygotes of this model are viable and fertile. In addition, based on the independently developed TurboKnockout fusion BAC recombination technology innovation, Cyagen can also provide disease models of popular point mutations based on this model, and can also provide customized services for different point mutations to meet the experimental needs of researchers in the pharmacodynamics of hemophilia B.