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 factorVIIgene (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 FVII deficiency, reduced , gene-altered mice, targeted gene replacement placed FVIII 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.