A mouse model for studying talpid3 and its role in hedgehog signalling

研究talpid3及其在hedgehog信号传导中的作用的小鼠模型

• 批准号: BB/E014496/1
• 负责人: Cheryll Tickle
• 金额: $ 32.12万
• 依托单位: University of Bath
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE014496%2F1
• 关键词: mouse; model; studying; talpid3; its

One of the biggest challenges in biology is to understand how a single cell, the fertilised egg, gives rise to organised arrays of cells and tissues and how all the different parts of the body develop in the right places. Recently we have discovered a new gene that is essential for proper development of the embryo. This stemmed from studying an inherited condition in chickens in which the embryos have many defects and die before development is complete. Further work in chick embryos revealed that this gene is required for responding to a cell-cell signalling molecule that controls the development of many parts of the embryo including the limb, brain and face. The cell-cell signalling molecule has also been associated with tumours. Now we have identified the gene responsible for producing the embryonic defects in the mutant chicken embryos, we wish to understand how the protein it encodes works. There are related human and mouse genes. In this project we wish to make mouse models in which we inactivate the related gene either in all the cells of the embryo or specifically in the developing limb. We will also generate embryos that are deficient both in this gene and also other genes in the hedgehog pathway so that we can work out how the genes interact. This will provide one route to exploring the function of the gene and the protein it encodes. Embryos from the mouse models can be frozen down and thus also create a long term resource for studying a crucial cell-cell signalling pathway in development.

生物学中最大的挑战之一是了解单个细胞（受精卵）如何产生有组织的细胞和组织阵列，以及身体的所有不同部分如何在正确的位置发育。最近我们发现了一种对于胚胎正常发育至关重要的新基因。这源于对鸡的一种遗传性疾病的研究，其中胚胎有许多缺陷并在发育完成之前死亡。对鸡胚胎的进一步研究表明，该基因是响应细胞间信号分子所必需的，该信号分子控制胚胎许多部分的发育，包括四肢、大脑和面部。细胞间信号分子也与肿瘤有​​关。现在我们已经确定了导致突变鸡胚胎中胚胎缺陷的基因，我们希望了解它编码的蛋白质是如何发挥作用的。有相关的人类和小鼠基因。在这个项目中，我们希望制作小鼠模型，在其中我们使胚胎所有细胞或特别是发育中肢体的相关基因失活。我们还将生成缺乏该基因以及刺猬通路中其他基因的胚胎，以便我们能够弄清楚这些基因如何相互作用。这将为探索该基因及其编码的蛋白质的功能提供一种途径。小鼠模型的胚胎可以被冷冻，从而为研究发育中的关键细胞间信号传导途径创造长期资源。