Tol2 gene trap integrations in the zebrafish amyloid precursor protein genes appa and aplp2 reveal accumulation of secreted APP at the embryonic veins.

Tol2 gene trap integrations in the zebrafish amyloid precursor protein genes appa and aplp2 reveal accumulation of secreted APP at the embryonic veins.
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DOI:
10.1002/dvdy.23725
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发表时间:
2012-02
影响因子:
2.5
通讯作者:
McGrail, Maura
McGrail, Maura
中科院分区:
生物学3区
文献类型:
--
作者:
Liao, Hsin-Kai;Wang, Ying;Watt, Kristin E. Noack;Wen, Qin;Breitbach, Justin;Kemmet, Chelsy K.;Clark, Karl J.;Ekker, Stephen C.;Essner, Jeffrey J.;McGrail, Maura

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淀粉样前体蛋白(APP)及其蛋白水解产物β淀粉样蛋白(Aβ)在阿尔茨海默病的发病机制中起着重要作用,已被广泛研究。然而,APP分泌胞外域(也是由蛋白水解切割产生的)的生物学作用尚不清楚。在这里,我们报告Tol 2红色荧光蛋白(RFP)转座子基因陷阱整合在斑马鱼淀粉样前体蛋白a(appa)和淀粉样前体蛋白2(aplp 2)基因。预计转座子整合破坏α和aplp 2基因,以主要产生与RFP融合的相应蛋白质的分泌胞外域。我们的研究结果表明,Appa-RFP和Aplp 2融合蛋白可能是从中枢神经系统分泌的,并在胚胎静脉中积累,不依赖于血流。斑马鱼的appa和aplp 2转座子插入等位基因将是有用的研究APP的分泌形式的生物学作用。
The single spanning transmembrane amyloid precursor protein (APP) and its proteolytic product, amyloid-beta (Aβ) peptide, have been intensely studied due to their role in the pathogenesis of Alzheimer’s disease. However, the biological role of the secreted ectodomain of APP, which is also generated by proteolytic cleavage, is less well understood. Here, we report Tol2 red fluorescent protein (RFP) transposon gene trap integrations in the zebrafish amyloid precursor protein a (appa) and amyloid precursor-like protein 2 (aplp2) genes. The transposon integrations are predicted to disrupt the appa and aplp2 genes to primarily produce secreted ectodomains of the corresponding proteins that are fused to RFP. Our results indicate the Appa-RFP and Aplp2 fusion proteins are likely secreted from the central nervous system and accumulate in the embryonic veins independent of blood flow. The zebrafish appa and aplp2 transposon insertion alleles will be useful for investigating the biological role of the secreted form of APP.
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