Joshi Powrnima, Liang Jennifer O, DiMonte Kristine, Sullivan John, Pimplikar Sanjay W
Department of Neurosciences, Lerner Research Institute, Cleveland Clinic NC-30, Cleveland, OH 44195, USA.
Dev Biol. 2009 Nov 1;335(1):1-11. doi: 10.1016/j.ydbio.2009.07.041. Epub 2009 Aug 4.
Amyloid precursor protein (APP) has been a focus of intense investigation because of its role in Alzheimer's disease (AD), however, its biological function remains uncertain. Loss of APP and APP-like proteins results in postnatal lethality in mice, suggesting a role during embryogenesis. Here we show that in a zebrafish model system, knock down of APP results in the generation of fish with dramatically reduced body length and a short, curly tail. In situ examination of gene expression suggests that the APP morphant embryos have defective convergent-extension movements. We also show that wild-type human APP rescues the morphant phenotype, but the Swedish mutant APP, which causes familial AD (fAD), does not rescue the developmental defects. Collectively, this work demonstrates that the zebrafish model is a powerful system to define the role of APP during embryonic development and to evaluate the functional activity of fAD mutant APP.
淀粉样前体蛋白（APP）因其在阿尔茨海默病（AD）中的作用而一直是深入研究的焦点，然而，其生物学功能仍不确定。APP及APP样蛋白的缺失会导致小鼠出生后死亡，这表明其在胚胎发育过程中发挥作用。在此我们表明，在斑马鱼模型系统中，敲低APP会导致鱼的体长显著缩短且尾巴短而卷曲。基因表达的原位检测表明，APP morphant胚胎的趋同延伸运动存在缺陷。我们还表明，野生型人类APP可挽救morphant表型，但导致家族性AD（fAD）的瑞典突变型APP不能挽救发育缺陷。总的来说，这项工作表明斑马鱼模型是一个强大的系统，可用于确定APP在胚胎发育过程中的作用，并评估fAD突变型APP的功能活性。
