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Elliot D. Rosen, Haifeng Xu, Zhong Liang, J. Andrew Martin, Mark Suckow, Francis J. Castellino

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

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.

Thrombosis and Haemostasis, Schattauer

Print ISSN: 0340-6245
Volume: 94, 09/2005
Pages: 493 - 497

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