Summary

It has been shown earlier that mice with a total targeted deletionof the factorVII gene (FVII-/- ) die perinatally,thereby precludingstudy of adult animals with this total deficiency. Consequently,mice producing very low levels of FVII were developedby targeted replacement of the wild-type (WT) murineFVII gene with its corresponding cDNA,under control of the tetracyclinetransactivator (tTA) promoter. When backcrossedinto the C57Bl/6 strain, unchallenged mice containing two replaced FVII^tTA alleles (FVII^tTA/tTA ) produce approximately 0.7% ofWT FVII levels, but yet live to adulthood despite displaying severelydownregulated overall thrombin production and spontaneouslydeveloping cardiac fibrosis at a young adult age.This genetically-altered mouse line provides an excellent animal modelto study consequences of a severe FVII deficiency in unchallengedmice and in mice subjected to a variety of experimentalchallenges.