ArticleBlood2014
A conditional knockout mouse model reveals endothelial cells as the principal and possibly exclusive source of plasma factor VIII.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
113 citing papers in PubMed, 182 citations in OpenAlex.
- Multiyear Factor VIII Expression after AAV Gene Transfer for Hemophilia A.The New England journal of medicine · 2021Trial
- A novel humanized FIX/FX hemophilia A mouse model for preclinical evaluation of FVIIIa-mimetic bispecific antibodies.Blood advances · 2026Article
- Article
- Defining the safety and efficacy of liver-directed AAV gene therapy using a human liver tissue-equivalent platform.Molecular therapy. Advances · 2026Article
- FVIII-containing platelets modulate immune responses and attenuate inhibitor development in hemophilia A mice.Haematologica · 2026Article
- Factor VIII originates primarily from anatomically distinct subsets of liver sinusoidal endothelial cells.Blood advances · 2026Article
- Investigative reporting on factor VIII whereabouts.Blood advances · 2026Article
- Biology of von Willebrand disease.Blood advances · 2026Review
- Divergent processing of FVIII light chain variants: secretory potentialHaematologica · 2026Article
- Missense and nonsense mutations and inhibitor development in patients with hemophilia A and B.Journal of thrombosis and thrombolysis · 2026Review
- Balancing Promise and Peril: Hemophilia Gene Therapy Insights.IUBMB life · 2026Review
- Advancements in CRISPR-basedFrontiers in genome editing · 2026Review
- Analyzing 6211 unique variants in the upgraded interactive FVIII web database reveals novel insights into hemophilia A.Blood vessels, thrombosis & hemostasis · 2025Article
- Loss of factor VIII in zebrafish rebalances antithrombin deficiency but has a limited bleeding diathesis.Blood advances · 2025Article
- Hemophilia A: An Ideal Disease for Prenatal Therapy.Prenatal diagnosis · 2025Review
- Current clinical applications of AAV-mediated gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Gene therapy for hemophilia - From basic science to first approvals of "one-and-done" therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Clinical, Laboratory, Molecular, and Reproductive Aspects of Combined Deficiency of Factors V and VIII.Seminars in thrombosis and hemostasis · 2025Review
- Thromboembolic Events in the Era of COVID-19: A Detailed Narrative Review.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2025Review
- Chemokine CXCL13 facilitates anti-FVIII inhibitory antibody development in hemophilia A patients and murine models.International immunopharmacology · 2024Article
53 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The cellular source of coagulation factor VIII (FVIII) remains controversial. Like many coagulation proteins, FVIII is produced in the liver, and FVIII synthesis has long been associated with hepatocytes. But extrahepatic synthesis also occurs, and mounting evidence suggests that hepatocytes are not responsible for FVIII production. To determine the tissue that synthesizes FVIII, we developed a Cre/lox-dependent conditional knockout (KO) model in which exons 17 and 18 of the murine factor VIII gene (F8) are flanked by loxP sites, or floxed (F8(F)). In cells expressing Cre-recombinase, the floxed sequence is deleted, resulting in F8(F→KO) gene inactivation. When F8(F) mice were crossed with various tissue-specific Cre strains, we found that hepatocyte-specific F8-KO mice are indistinguishable from controls, whereas efficient endothelial-KO models display a severe hemophilic phenotype with no detectable plasma FVIII activity. A hematopoietic Cre model was more equivocal, so experimental bone marrow transplantation was used to examine hematopoietic FVIII synthesis. FVIII(null) mice that received bone marrow transplants from wild-type donors were still devoid of plasma FVIII activity after hematopoietic donor cell engraftment. Our results indicate that endothelial cells are the predominant, and possibly exclusive, source of plasma FVIII.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.