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Thromb Haemost. 2005 Sep;94(3):493-7.

Generation of genetically-altered mice producing very low levels of coagulation factorVII.

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  • 1W. M. Keck Center forTransgene Research, Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46202, USA. edrosen@iupui.edu

Abstract

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 FYII gene with its corresponding cDNA, under control of the tetracycline transactivator (tTA) promoter. When backcrossed into the C57BI/6 strain, unchallenged mice containing two replaced FVII(tTA) alleles (FVII(tTA/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.

PMID:
16268461
[PubMed - indexed for MEDLINE]
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