Targeted disruption of mouse fibroblast activation protein
Targeted disruption of mouse fibroblast activation protein
复制标题
DOI：
10.1128/mcb.20.3.1089-1094.2000
复制
发表时间：
2000-02-01
影响因子：
5.3
通讯作者：
Schnapp, A
中科院分区：
文献类型：
--
作者：
Niedermeyer, J;Kriz, M;Schnapp, A
人成纤维细胞活化蛋白 (FAP) 是丝氨酸脯氨酰寡肽酶家族的成员，是一种 II 型细胞表面糖蛋白，由活跃组织重塑区域的成纤维细胞选择性表达，例如胚胎间质、伤口愈合区域、妊娠子宫和上皮癌的反应性基质。已在小鼠和非洲爪蟾中鉴定出 FAP 的同源物。 FAP 是一种双特异性酶，在体外可充当二肽基肽酶和胶原酶。为了探索FAP在体内的作用，通过同源重组产生Fap(-/-)小鼠。 RNase 保护分析和逆转录 PCR 证实小鼠胚胎组织中不存在全长 Fap 转录本。免疫组织化学法未在Fap(-/-)动物中检测到FAP蛋白，也未发现FAP特异性二肽基肽酶活性。我们报告 Fap(-/-) 小鼠具有生育能力，没有表现出明显的发育缺陷，并且癌症易感性没有总体变化。
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.