Tol2 基因捕获整合在斑马鱼淀粉样前体蛋白基因 appa 和 aplp2 中，揭示了分泌型 APP 在胚胎静脉中的积累。
Tol2 gene trap integrations in the zebrafish amyloid precursor protein genes appa and aplp2 reveal accumulation of secreted APP at the embryonic veins.
机构信息
Department of Genetics, Development and Cell Biology, Iowa State University, Ames, Iowa 50011, USA.
出版信息
Dev Dyn. 2012 Feb;241(2):415-25. doi: 10.1002/dvdy.23725.
BACKGROUND
The single spanning transmembrane amyloid precursor protein (APP) and its proteolytic product, amyloid-beta (Ab) 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.
RESULTS
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.
CONCLUSIONS
The zebrafish appa and aplp2 transposon insertion alleles will be useful for investigating the biological role of the secreted form of APP.
背景
单一跨膜淀粉样前体蛋白 (APP) 及其蛋白水解产物淀粉样-β (Ab) 肽因其在阿尔茨海默病发病机制中的作用而受到广泛研究。然而，APP 的分泌型胞外结构域（也通过蛋白水解切割产生）的生物学作用了解较少。在这里，我们报告了在斑马鱼淀粉样前体蛋白 a (appa) 和淀粉样前体样蛋白 2 (aplp2) 基因中 Tol2 红色荧光蛋白 (RFP) 转座子基因捕获整合。转座子整合预计会破坏 appa 和 aplp2 基因，主要产生相应蛋白的分泌型胞外结构域，与 RFP 融合。
结果
我们的结果表明，Appa-RFP 和 Aplp2 融合蛋白可能从中枢神经系统分泌，并独立于血流在胚胎静脉中积累。
结论
斑马鱼 appa 和 aplp2 转座子插入等位基因将有助于研究 APP 分泌形式的生物学作用。
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