B6-F8 KO Mice

Catalog Number: I001219

Strain Name: C57BL/6JCya-F8em2/Cya

Genetic Background: C57BL/6JCya

 

Strain Description

The F8 gene encodes coagulation factor VIII (FVIII), a large plasma glycoprotein crucial for the intrinsic pathway of blood coagulation. This gene generates two alternatively spliced transcripts, with the larger isoform, variant a, forming a non-covalent complex with von Willebrand factor (vWF) that circulates in plasma. Under normal physiological conditions, when a blood vessel is injured, platelets and clotting factors aggregate at the site of injury to form a blood clot and prevent further bleeding. In this process, FVIII functions as a cofactor, working synergistically with activated factor IX (FIXa) to activate factor X (FX), subsequently generating fibrin and stabilizing the blood clot. Deficiency of the F8 gene leads to hemophilia A (HA), an X-linked recessive bleeding disorder that primarily affects males. Patients often present with spontaneous or post-traumatic bleeding that may be difficult to control, with severe cases risking disability or life-threatening complications due to internal bleeding and joint hemorrhage. Clinically, exogenous FVIII supplementation is effective in managing hemophilia A symptoms. In recent years, advances in gene therapy and gene editing have offered new hope for HA treatment, aiming for long-term or permanent cure by repairing or replacing the defective F8 gene.

The B6-F8 KO mouse is a hemophilia A (HA) research model developed through gene-editing techniques, where the murine F8 gene, homologous to the human F8 gene, is knocked out. Studies have shown that homozygous F8 knockout mice are viable and develop normally [1]. Since the murine F8 gene is located on the X chromosome, hemizygous male and homozygous female B6-F8 KO mice exhibit a consistent phenotype with significantly lower FVIII activity compared to wild-type mice, prolonged clotting time, and a classic hemophilia A phenotype [1].

Strain Strategy


Figure 1. Gene editing strategy of B6-F8 KO mice. The murine F8 gene, located on the X chromosome, was modified by gene editing to knock out exons 2–3.

Application

  • Investigation of hemophilia A (HA) pathogenesis and the development and evaluation of therapeutic agents;
  • Studies on the coagulation cascade process.

 

References
[1]Bi L, Lawler AM, Antonarakis SE, High KA, Gearhart JD, Kazazian HH Jr. Targeted disruption of the mouse factor Ⅷ gene produces a model of haemophilia A. Nat Genet. 1995 May;10(1):119-21.