Generation of genetically-altered mice producing very low levels of coagulation factorVII.
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 FYII 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 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.
Rosen
Elliot D
ED
W. M. Keck Center forTransgene Research, Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46202, USA. edrosen@iupui.edu
Xu
Haifeng
H
Liang
Zhong
Z
Martin
J Andrew
JA
Suckow
Mark
M
Castellino
Francis J
FJ
D000818:Animals; D000990:Antithrombin III; D003001:Cloning, Molecular; D003094:Collagen / Q000378:metabolism; D015536:Down-Regulation; D005167:Factor VII / Q000235:genetics* / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005822:Genetic Vectors; D005838:Genotype; D006487:Hemostasis / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010314:Partial Thromboplastin Time; D010447:Peptide Hydrolases / Q000097:blood; D011517:Prothrombin Time; D012333:RNA, Messenger / Q000378:metabolism; D013752:Tetracycline / Q000008:administration & dosage / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D005167:Factor VII; D005337:Fibrin; D003094:Collagen; D010447:Peptide Hydrolases; D013752:Tetracycline