F9 KO Mouse

Hemophilia is a group of genetic bleeding disorders that affect the blood’s ability to clot. The common feature of this disease is the generation of abnormal clotting factors, which leads to prolonged clotting time and increased risk of bleeding after minor injuries. In severe cases, spontaneous bleeding can occur even without obvious trauma. As an X-linked recessive disorder, Hemophilia B is more common in males, with approximately 1 in every 30,000 newborn males worldwide being affected ^[1]. Hemophilia B is caused by mutations in the F9 (FIX) gene, which leads to a deficiency of clotting factor IX. The severity of the disease is usually correlated with the activity level of factor IX in the blood plasma. Mild patients (IX factor activity >5%, >0.05 IU/mL) do not experience spontaneous bleeding, but the amount of bleeding after injury or surgery may increase. Moderate patients (IX factor activity 1%-5%, 0.01-0.05 IU/mL) rarely experience spontaneous bleeding, but even minor injuries can cause prolonged bleeding. Severe patients (IX factor activity <1%, <0.01 IU/mL) experience spontaneous bleeding, soft tissue or joint bleeding, and severe subcutaneous hematomas ^[2]. According to the Centers for Disease Control and Prevention (CDC) in the United States, severe Hemophilia B patients account for 30%-40% of all diagnosed patients ^[3].

The F9 gene encodes coagulation factor IX, a vitamin K-dependent serine protease that plays a key role in the intrinsic coagulation pathway. Factor IX circulates in the blood as an inactive zymogen and is converted to its active form, factor IXa, by the cleavage of its activation peptide by factor XIa. Factor IXa then interacts with Ca2+ ions, membrane phospholipids, and factor Ⅷ to activate factor X in the coagulation cascade. The body can normally stop bleeding when the levels of factors Ⅷ and IX are ≥50% of normal values ^[4]. The deficiency of the F9 gene can lead to a clotting disorder with insufficient factor IX, causing X-linked recessive hemophilia B.

F9 KO mice are Hemophilia B disease models constructed by knocking out the mouse F9 gene. F9 KO mice lack F9 mRNA expression and exhibit coagulation dysfunction and other Hemophilia B-related phenotypes. They can be used to study the genetic mechanisms and clinical phenotypes of Hemophilia B in humans and to assist in developing, screening, and evaluating therapeutic drugs. The homozygotes are viable and fertile. Tail docking may lead to significant bleeding. Immediate hemostasis, such as cauterizing the tail incision, is advised to prevent health complications in homozygous mice. Usually, ear tags are applied to mice at 2 to 3 weeks of age (a small notch is made with scissors for identification). After tail clipping for genotyping, the tail wound should be promptly cauterized (using metal forceps heated with an alcohol lamp) to prevent fatal bleeding. Following cauterization, place the mouse in a clean cage to prevent wound infection and add environmental enrichment.