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Molecular and Cellular Biology, February 2000, p. 1089-1094, Vol. 20, No. 3
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Targeted Disruption of Mouse Fibroblast Activation Protein

J. Niedermeyer,1,dagger M. Kriz,2 F. Hilberg,2 P. Garin-Chesa,1 U. Bamberger,1 M. C. Lenter,1 J. Park,1 B. Viertel,3 H. Püschner,3 M. Mauz,3 W. J. Rettig,1 and A. Schnapp1,*

Department of Oncology Research1 and Department of Nonclinical Drug Safety,3 Boehringer Ingelheim Pharma KG, 88397 Biberach, Germany, and Department of Molecular Biology, Boehringer Ingelheim Austria, A-1121 Vienna, Austria2

Received 25 October 1999/Accepted 27 October 1999

Human fibroblast activation protein (FAP), a member of the serine prolyl oligopeptidase family, is a type II cell surface glycoprotein selectively expressed by fibroblastic cells in areas of active tissue remodeling, such as the embryonic mesenchyme, areas of wound healing, the gravid uterus, and the reactive stroma of epithelial cancers. Homologues of FAP have been identified in the mouse and Xenopus laevis. FAP is a dual-specificity enzyme that acts as a dipeptidyl peptidase and collagenase in vitro. To explore the role of FAP in vivo, Fap-/- mice were generated by homologous recombination. RNase protection analysis and reverse transcription-PCR confirmed the absence of full-length Fap transcripts in mouse embryonic tissues. No FAP protein was detected in Fap-/- animals by immunohistochemistry, and no FAP-specific dipeptidyl peptidase activity was found. We report that Fap-/- mice are fertile, show no overt developmental defects, and have no general change in cancer susceptibility.


* Corresponding author. Mailing address: Department of Oncology Research, Boehringer Ingelheim Pharma KG, 88397 Biberach an der Riss, Germany. Phone: 49 7351 54 5240. Fax: 49 7351 54 5148. E-mail: andreas.schnapp{at}bc.boehringer-ingelheim.com.

dagger Present address: Research Institute for Molecular Pathology, A-1030 Vienna, Austria.


Molecular and Cellular Biology, February 2000, p. 1089-1094, Vol. 20, No. 3
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



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