ArticleJournal of thrombosis and haemostasis : JTH2016
Characterization of a genetically engineered mouse model of hemophilia A with complete deletion of the F8 gene.
Article in Journal of thrombosis and haemostasis : JTH, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 17 citations in OpenAlex.
- A novel humanized FIX/FX hemophilia A mouse model for preclinical evaluation of FVIIIa-mimetic bispecific antibodies.Blood advances · 2026Article
- Antimetabolites synergize with non-genotoxic antibody drug conjugate conditioning in hematopoietic stem cell lentiviral gene therapy.Molecular therapy. Advances · 2026Article
- Defining the Role of Marginal Zone B Cells in FVIII Inhibitor Development.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Article
- AAV mediated repression of Neat1 lncRNA combined with F8 gene augmentation mitigates pathological mediators of joint disease in haemophilia.Journal of cellular and molecular medicine · 2024Article
- Generation of Mouse Model of Hemophilia A by Introducing Novel Mutations, Using CRISPR/Nickase Gene Targeting System.Cell journal · 2023Article
- Article
- Defenestrated endothelium delays liver-directed gene transfer in hemophilia A mice.Blood advances · 2022Article
- Adeno-associated virus-mediated expression of activated factor V (FVa) for hemophilia phenotypic correction.Frontiers in medicine · 2022Article
- Neutralizing Antibodies Against Factor VIII Can Occur Through a Non-Germinal Center Pathway.Frontiers in immunology · 2022Article
- Development of a novel fully functional coagulation factor VIII with reduced immunogenicity utilizing an in silico prediction and deimmunization approach.Journal of thrombosis and haemostasis : JTH · 2021Article
- A Foundational Study for NormalInternational journal of molecular sciences · 2020Article
- Fc Gamma Receptors and Complement Component 3 Facilitate Anti-fVIII Antibody Formation.Frontiers in immunology · 2020Article
- Reduced bone formation in males and increased bone resorption in females drive bone loss in hemophilia A mice.Blood advances · 2019Article
- Marginal zone B cells are critical to factor VIII inhibitor formation in mice with hemophilia A.Blood · 2017Article
- Gene Delivery of Activated Factor VII Using Alternative Adeno-Associated Virus Serotype Improves Hemostasis in Hemophiliac Mice with FVIII Inhibitors and Adeno-Associated Virus Neutralizing Antibodies.Human gene therapy · 2017Article
- Current animal models of hemophilia: the state of the art.Thrombosis journal · 2016Review
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
unlabelledESSENTIALS: Anti-factor VIII (FVIII) inhibitory antibody formation is a severe complication in hemophilia A therapy. We genetically engineered and characterized a mouse model with complete deletion of the F8 coding region. F8(TKO) mice exhibit severe hemophilia, express no detectable F8 mRNA, and produce FVIII inhibitors. The defined background and lack of FVIII in F8(TKO) mice will aid in studying FVIII inhibitor formation.
backgroundThe most important complication in hemophilia A treatment is the development of inhibitory anti-Factor VIII (FVIII) antibodies in patients after FVIII therapy. Patients with severe hemophilia who express no endogenous FVIII (i.e. cross-reacting material, CRM) have the greatest incidence of inhibitor formation. However, current mouse models of severe hemophilia A produce low levels of truncated FVIII. The lack of a corresponding mouse model hampers the study of inhibitor formation in the complete absence of FVIII protein.
objectivesWe aimed to generate and characterize a novel mouse model of severe hemophilia A (designated the F8(TKO) strain) lacking the complete coding sequence of F8 and any FVIII CRM.
methodsMice were created on a C57BL/6 background using Cre-Lox recombination and characterized using in vivo bleeding assays, measurement of FVIII activity by coagulation and chromogenic assays, and anti-FVIII antibody production using ELISA.
resultsAll F8 exonic coding regions were deleted from the genome and no F8 mRNA was detected in F8(TKO) mice. The bleeding phenotype of F8(TKO) mice was comparable to E16 mice by measurements of factor activity and tail snip assay. Similar levels of anti-FVIII antibody titers after recombinant FVIII injections were observed between F8(TKO) and E16 mice.
conclusionsWe describe a new C57BL/6 mouse model for severe hemophilia A patients lacking CRM. These mice can be directly bred to the many C57BL/6 strains of genetically engineered mice, which is valuable for studying the impact of a wide variety of genes on FVIII inhibitor formation on a defined genetic background.
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