 | FIBRINOGEN: XVIth INTERNATIONAL FIBRINOGEN WORKSHOP
Copyright © 2001 by the New York Academy of Sciences
description
Annals of the New York Academy of Sciences 936:276-290 (2001)
© 2001 New York Academy of Sciences
Genetic Manipulation of Fibrinogen and Fibrinolysis in Mice
JAY L. DEGEN,
ANGELA F. DREW,
JOSEPH S. PALUMBO,
KEITH W. KOMBRINCK,
JORGE A. BEZERRA,
MARY JO S. DANTON,
KENN HOLMBÄCK AND
THEODORE T. SUH
Children's Hospital Research Foundation and University of Cincinnati
College of Medicine, Cincinnati, Ohio, USA
Address for correspondence: J. L. Degen, Ph.D., Children's Hospital Research Foundation, Children's Hospital Medical Center, IDR - NRB Room 2042, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3039, USA. Voice: 513-636-4679;fax: 513-636-4317
degenjl{at}chmcc.org
Vascular integrity is maintained by a sophisticated system of circulating and cell associated hemostatic factors that control local platelet deposition, the conversion of soluble fibrinogen to an insoluble fibrin polymer, and the dissolution of fibrin matrices. However, hemostatic factors are likely to be biologically more important than merely maintaining vascular patency and controlling blood loss. Specific hemostatic factors have been associated with a wide spectrum of physiological processes, including development, reproduction, tissue remodeling, wound repair, angiogenesis, and the inflammatory response. Similarly, it has been proposed that hemostatic factors are important determinants of a variety of pathological processes, including vessel wall disease, tumor dissemination, infectious disease, and inflammatory diseases of the joint, lung, and kidney. The development of gene targeted mice either lacking or expressing modified forms of selected hemostatic factors has provided a valuable opportunity to test prevailing hypotheses regarding the biological roles of key coagulation and fibrinolytic system components in vivo. Genetic analyses of fibrin(ogen) and its interacting factors in transgenic mice have proven to be particularly illuminating, often challenging long standing concepts. This review summarizes the key findings made in recent studies of gene targeted mice with single and combined deficits in fibrinogen and fibrinolytic factors. Studies illustrating the role and interplay of these factors in disease progression are highlighted.
Key Words: Fibrogen-deficient mice • Gene targeting • Fibrinolysis • Fibrin • Hemostasis
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