Factor IX: Insights from knock-out and genetically engineered mice

Paul E. Monahan

doi:10.1160/TH08-04-0262

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 100(04): 563-575
DOI: 10.1160/TH08-04-0262

Theme Issue Article

Schattauer GmbH

Factor IX: Insights from knock-out and genetically engineered mice

Paul E. Monahan

¹Department of Pediatrics, Gene Therapy Center, and the Harold R. Roberts Comprehensive Hemophilia Diagnostic and Treatment Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

› Author Affiliations

Abstract

Summary

The study of coagulation factors has been rapidly advanced by studies performed in genetically engineered mouse strains. Investigation of factor IX (FIX) has benefited from excellent genedeleted mouse models that recapitulate many of the features of human haemophilia B. Moreover, advanced positional cloning techniques and availability of technology to allow not only knock-out mice, but also knock-in and knock-down mice, provide new opportunities to observe genotype-phenotype and structure-function correlations regarding FIX, as well as the interaction of FIX with inflammatory, immune, and tissue repair systems. In this paper, available FIX knock-out mice and additional haemophilia B mouse models are reviewed specifically in regards to observations these models have facilitated concerning: factor IX gene expression and factor IX protein pharmacokinetics; the role of FIX in haemostasis, thrombosis and wound healing; insights into coagulation FIX arising out of gene therapy applications in haemophilia mouse models; immunology of tolerance or loss of tolerance of FIX and inhibitor antibody formation.

Keywords

Factor IX - mouse model - transgenic mouse - haemophilia B - gene therapy

Full Text

References

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