help button home button Am J Pathol Epitomics Buy 2 Antibodies Get 1 Free Special Offer
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tian, B.
Right arrow Articles by Henke, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tian, B.
Right arrow Articles by Henke, C.
(American Journal of Pathology. 2003;163:789-801.)
© 2003 American Society for Investigative Pathology

Animal Model

An HSV-TK Transgenic Mouse Model to Evaluate Elimination of Fibroblasts for Fibrosis Therapy

Bin Tian, Lei Han, Jill Kleidon and Craig Henke

From the Department of Medicine, University of Minnesota, Minneapolis, Minnesota

Pathological fibroproliferation after tissue injury is harmful and may lead to organ dysfunction. Unfortunately, fibroproliferative diseases remain intractable to current therapeutic strategies. Thus, new therapeutic approaches are needed. One possible approach is to promote resolution of physiological fibroproliferation that follows injury before it becomes pathological by activating apoptosis selectively in fibrotic lesions. However, it is not known whether selective elimination of fibroblasts will prevent fibrosis or impede repair or worsen injury by eliminating topographic signals essential to organ reconstitution. To address this question, a tractable in vivo model system is needed in which fibroblasts can be targeted to undergo apoptosis at a chosen time and place. We developed transgenic mice expressing HSV-TK from the type I collagen promoter to determine whether selective elimination of fibroblasts actively forming fibrotic lesions is an effective therapeutic strategy for fibroproliferative disorders. The transgene renders fibroblasts actively forming fibrotic tissue susceptible to ganciclovir. To validate the transgenic model we examined whether administration of ganciclovir prevents the development of fibrosis in sponges implanted subcutaneously in the backs of the transgenic mice. We demonstrate that fibroblasts/myofibroblasts isolated from sponges express HSV-TK protein and are selectively ablated by ganciclovir in vitro. In adult transgenic mice, ganciclovir treatment attenuated the development of fibrotic tissue in the sponges both biochemically and histologically. We conclude that this transgenic model system is an ideal approach to determine whether targeted ablation of fibroblasts is an effective therapeutic strategy for fibrotic diseases.




This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
F. Zeng, M.-j. Chen, D. A. Baldwin, Z.-j. Gong, J.-b. Yan, H. Qian, J. Wang, X. Jiang, Z.-r. Ren, D. Sun, et al.
Multiorgan engraftment and differentiation of human cord blood CD34+Lin- cells in goats assessed by gene expression profiling
PNAS, May 16, 2006; 103(20): 7801 - 7806.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2003 by the American Society for Investigative Pathology.