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

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 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.

Keywords

FVII deficiency - reduced thrombogenesis - gene-altered mice - targeted gene replacement

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