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

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

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

It has been shown earlier that mice with a total targeted deletion of the factor VII 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 C57BI/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.

Original languageEnglish (US)
Pages (from-to)493-497
Number of pages5
JournalThrombosis and Haemostasis
Volume94
Issue number3
DOIs
StatePublished - Sep 1 2005

Keywords

  • FVII deficiency
  • Gene-altered mice
  • Reduced thrombogenesis
  • Targeted gene replacement

ASJC Scopus subject areas

  • Hematology

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