Analysis of the function of the presenilin genes during embryogenesis.

早老素基因对人类正常的心理健康至关重要。早老素基因的有害变化是60%的家族遗传阿尔茨海默病的根本原因。早发（阿尔茨海默病）和所有阿尔茨海默病的10%。正常的早老素基因也是正确胚胎发育所必需的。有证据表明，早老素基因产生的蛋白质与其他蛋白质（如Notch基因产生的蛋白质）相互作用。Notch基因的改变也会导致痴呆和发育缺陷。然而，尽管它们的重要性显而易见，我们对早老素和Notch基因的功能和相互作用知之甚少！我们想了解早老素基因如何与Notch基因和其他对正常胚胎发育重要的基因相互作用。为了研究这个问题，我们使用了一种小型淡水鱼斑马鱼的卵。这些卵很容易获得（雌性斑马鱼每周生产数百个），可接近，并且透明，可以观察到发育中的斑马鱼卵中的每个细胞！它们的发育速度也比人类快100倍！在我们的实验中，我们将产生针对斑马鱼早老素和Notch基因蛋白产物的抗体，然后用这些抗体来观察早老素和Notch蛋白之间的相互作用。我们将观察胚胎中早老素蛋白水平的变化如何影响Notch基因的功能，并试图发现受这种变化影响的其他基因。这项工作对于理解基因在胚胎发育过程中如何相互作用来创造我们的身体是很重要的。此外，由于基因在胚胎发育和成人发育过程中通常以相似的方式相互作用，我们的发现将有助于我们了解早老素基因的变化导致阿尔茨海默病时出现的问题。

The presenilin genes are essential for normal human mental health. Deleterious changes in presenilin genes are the root cause of 60% of Alzheimers Disease that is inherited within families (ie. Oearly onsetO Alzheimers disease) and of 10% of all Alzheimers disease. Normal presenilin genes are also necessary for correct embryo development. There is evidence that the proteins produced by the presenilin genes interact with other proteins such as those produced by the Notch genes. Changes in Notch genes can also produce dementia and developmental defects. However, despite their obvious importance, we know little about how presenilin and Notch genes function and interact! We want to understand how presenilin genes interact with Notch genes and any other genes that are important for normal embryo development. To investigate this we are using the eggs of a small, freshwater fish, the zebrafish. These eggs are easily available (hundreds are produced by a female zebrafish every week), accessible and, being transparent, every cell in a developing zebrafish egg can be observed! They also develop about one hundred times faster that a human! In our experiments we will produce antibodies to the protein products of the presenilin and Notch genes of zebrafish and then use these to observe interactions between the presenilin and Notch proteins. We will observe how changes in the levels of presenilin protein in an embryo affect the function of the Notch genes and we will attempt to discover other genes that are affected by such changes. This work will be important for understanding how genes interact to create our bodies during embryo development. Also, since genes typically interact in similar ways during embryo development and in adults, the discoveries that we make will help us to understand what goes wrong when changes in the presenilin genes cause Alzheimers disease.