TY - JOUR
T1 - Generation of genetically-altered mice producing very low levels of coagulation factor VII
AU - Rosen, Elliot D.
AU - Xu, Haifeng
AU - Liang, Zhong
AU - Martin, Andrew J.
AU - Suckow, Mark
AU - Castellino, Francis J.
PY - 2005/9
Y1 - 2005/9
N2 - 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.
AB - 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.
KW - FVII deficiency
KW - Gene-altered mice
KW - Reduced thrombogenesis
KW - Targeted gene replacement
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U2 - 10.1160/TH05-05-0337
DO - 10.1160/TH05-05-0337
M3 - Article
C2 - 16268461
AN - SCOPUS:24944446824
SN - 0340-6245
VL - 94
SP - 493
EP - 497
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
IS - 3
ER -