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Thromb Haemost 2000; 84(05): 826-832
DOI: 10.1055/s-0037-1614124
Review Article
Schattauer GmbH

Characterization of Antibodies Induced by Human Factor VIII in a Murine Knockout Model of Hemophilia A

Birgit M. Reipert
1   From the Baxter Hyland Immuno, Vienna, Austria
,
Rafi U. Ahmad
1   From the Baxter Hyland Immuno, Vienna, Austria
,
Peter L. Turecek
1   From the Baxter Hyland Immuno, Vienna, Austria
,
Hans P. Schwarz
1   From the Baxter Hyland Immuno, Vienna, Austria
› Author AffiliationsWe are grateful to Eleonore Gschaider, Cornelia-Esther Wagner, Doris Nottny and Georgios Kalliontzis for technical assistance. We also thank Howard M. Reisner for his critical review and Kathryn Nelson for editing the manuscript.
Further Information

Publication History

Received 02 March 2000

Accepted after resubmission 30 May 2000

Publication Date:
13 December 2017 (online)

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Summary

To investigate the usefulness of factor VIII (FVIII) knockout mice as an animal model of hemophilia A, we characterized the antibody response in FVIII knockout mice to recombinant human FVIII, administered intravenously or subcutaneously with or without adjuvant, and compared results to those in normal mice. Anti-factor VIII antibodies were detected after both intravenous and subcutaneous administration, with the highest titers after subcutaneous administration plus adjuvant. Depending on the administration strategy, knockout mice formed antibodies more rapidly and developed higher titers of inhibitory antibodies (Bethesda) than normal mice, suggesting differences in epitope specificity. Blotting thrombin cleavage products separated by gel electrophoresis showed that both strains developed antibodies against the nonfunctional B domain as well as against functional domains of factor VIII. The antibodies were mainly of the IgG1 subclass and resembled type I antibodies in hemophilia A.

Key words

Hemophilia A - animal model - knockout mice - factor VIII - antibodies
 

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