Targeted disruption of mouse fibroblast activation protein.
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.
Niedermeyer
J
J
Department of Oncology Research, Boehringer Ingelheim Pharma KG, 88397 Biberach, Germany.
Kriz
M
M
Hilberg
F
F
Garin-Chesa
P
P
Bamberger
U
U
Lenter
M C
MC
Park
J
J
Viertel
B
B
Püschner
H
H
Mauz
M
M
Rettig
W J
WJ
Schnapp
A
A
D000375:Aging; D000818:Animals; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D003433:Crosses, Genetic; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D005314:Embryonic and Fetal Development; D010450:Endopeptidases; D005260:Female; D005298:Fertility; D005347:Fibroblasts / Q000378:metabolism; D018093:Gelatinases; D006133:Growth Substances / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008648:Mesoderm / Q000166:cytology / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D011995:Recombination, Genetic; D015183:Restriction Mapping; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D013234:Stem Cells; D014158:Transcription, Genetic; D014982:Xenopus laevis; D000099167:Fibroblast Activation Protein Alpha
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D010450:Endopeptidases; D018093:Gelatinases; D006133:Growth Substances; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha