Thromb Haemost 2005; 94(03): 493-497
DOI: 10.1160/TH05-05-0337
Rapid and Short Communication
Schattauer GmbH

Generation of genetically-altered mice producing very low levels of coagulation factor VII

Elliot D. Rosen
1   W. M. Keck Center for Transgene Research
2   Department of Chemistry and Biochemistry
4   Department of Medical and Molecular Genetics and Indiana Center for Vascular Biology and Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
,
Haifeng Xu
1   W. M. Keck Center for Transgene Research
2   Department of Chemistry and Biochemistry
,
Zhong Liang
1   W. M. Keck Center for Transgene Research
4   Department of Medical and Molecular Genetics and Indiana Center for Vascular Biology and Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
,
J. Andrew Martin
1   W. M. Keck Center for Transgene Research
2   Department of Chemistry and Biochemistry
,
Mark Suckow
3   Friemann Life Science Center, University of Notre Dame, Notre Dame, Indiana, USA
,
Francis J. Castellino
1   W. M. Keck Center for Transgene Research
2   Department of Chemistry and Biochemistry
› Author Affiliations

Financial support: This work was supported by grants HL060081 (to EDR) and HL074750 (to FJC) from the NIH
Further Information

Publication History

Received: 16 May 2005

Accepted after major revision: 27 June 2005

Publication Date:
07 December 2017 (online)

Preview

Summary

It has been shown earlier that mice with a total targeted deletion of the factorVII gene (FVII-/-) die perinatally, thereby precluding study of adult animals with this total deficiency. Consequently, mice producing very low levels of FVII were developed by targeted replacement of the wild-type (WT) murine FVII gene with its corresponding cDNA, under control of the tetracycline transactivator (tTA) promoter. When backcrossed into the C57Bl/6 strain, unchallenged mice containing two replaced FVIItTA alleles (FVIItTA/tTA) produce approximately 0.7% of WT FVII levels, but yet live to adulthood despite displaying severely downregulated overall thrombin production and spontaneously developing cardiac fibrosis at a young adult age. This genetically- altered mouse line provides an excellent animal model to study consequences of a severe FVII deficiency in unchallenged mice and in mice subjected to a variety of experimental challenges.