Document Detail


A novel transgenic mouse model of hyperfibrinogenemia.
MedLine Citation:
PMID:  11521996     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hyperfibrinogenemia is a risk predictor in several diseases, including cardiovascular disease. Nevertheless, it remains unknown whether elevated fibrinogen has an etiologic role in or is a reflection of disease pathogenesis, or both. To examine this question, we generated a mouse model of hyperfibrinogenemia. We isolated the mouse fibrinogen locus, containing the three fibrinogen genes, in a single P1 clone. This approximately 100 kb clone was injected into C57Bl/6J zygotes. Three transgenic lines were identified, two with elevated fibrinogen, 1.4- and 1.7-fold relative to normal. We characterized the line with the higher level. Northern blots of total RNA showed transgene expression was liver specific, and the message levels were 2- to 3-fold enhanced. Fibrinogen in transgenic mice was normal in both immunologic and clotting assays. Our data indicate that over-expression of all three fibrinogen genes is necessary to achieve hyperfibrinogenemia. We saw no increase in mortality or morbidity, no gross abnormalities in the organs, and no histologic differences in lung, liver, spleen or kidney, in transgenic mice relative to normal littermates. We conclude that elevated fibrinogen did not cause disease in mice. We anticipate that breeding these mice to other mouse models of disease will demonstrate whether hyperfibrinogenemia has a role in the initiation or progression of symptomatic disease.
Authors:
A A Gulledge; F Rezaee; J H Verheijen; S T Lord
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Thrombosis and haemostasis     Volume:  86     ISSN:  0340-6245     ISO Abbreviation:  Thromb. Haemost.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-08-27     Completed Date:  2002-08-02     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7608063     Medline TA:  Thromb Haemost     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  511-6     Citation Subset:  IM    
Affiliation:
University of North Carolina at Chapel Hill, 27599-7525, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cloning, Molecular
Disease Models, Animal*
Fibrinogen / adverse effects,  genetics,  metabolism*
Liver / metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic*
Organ Specificity
RNA / metabolism
Transgenes / genetics
Grant Support
ID/Acronym/Agency:
HL52706/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
63231-63-0/RNA; 9001-32-5/Fibrinogen
Comments/Corrections
Comment In:
Thromb Haemost. 2001 Aug;86(2):509-10   [PMID:  11521995 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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