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CSF1R in homeostasis and immunity

CSF1R 在体内平衡和免疫中的作用

基本信息

批准号：
MR/M019969/1
负责人：
David Hume
金额：
$ 104.37万
依托单位：
University of Edinburgh
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2015
资助国家：
英国
起止时间：
2015 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FM019969%2F1
关键词：
CSF1R homeostasis immunity

项目摘要

The sequence of DNA in the genome of a mammal such as a mouse or a human contains a code that specifies the way that a body develops and grows. Specialised types of cells use only parts of the genome to generate their function; for example a red blood cell must produce the proteins (globin) that are needed to carry oxygen, where these proteins are not needed in the liver. This project is concerned with deciphering the code within DNA that ensures that the genes that code for particular products are produced in the right place at the right time. It deals specifically with a model gene, the CSF1R gene, which is needed for the production and function of large white blood cells called macrophages. The only we can dissect the function of individual elements of the code is to remove them from the genome. In this project we will use mouse transgenic technologies to determine what happens to CSF1R is we take out part of the code that controls where and when it is produced. The second part of the project applies the tools generated to determine the function of macrophages. These cells are found in every organ in the body. They are part of the body's defense against infections, but they also contribute to repair and regeneration. Their function is controlled by the CSF1R gene, and we are developing therapies that target that gene. The mouse models will enable us to identify and test new therapies.

哺乳动物（如小鼠或人类）基因组中的DNA序列包含一个指定身体发育和生长方式的代码。特殊类型的细胞仅使用部分基因组来产生其功能;例如，红细胞必须产生携带氧气所需的蛋白质（珠蛋白），而这些蛋白质在肝脏中不需要。该项目致力于破译DNA中的密码，以确保编码特定产品的基因在正确的时间在正确的地点产生。它专门涉及一个模型基因，CSF 1 R基因，这是需要的生产和功能的大白色血细胞称为巨噬细胞。我们唯一能剖析密码中单个元素的功能的方法就是将它们从基因组中移除。在这个项目中，我们将使用小鼠转基因技术来确定CSF 1 R发生了什么，我们取出了控制何时何地产生的部分代码。该项目的第二部分应用生成的工具来确定巨噬细胞的功能。这些细胞存在于身体的每个器官中。它们是身体防御感染的一部分，但它们也有助于修复和再生。它们的功能由CSF 1 R基因控制，我们正在开发针对该基因的疗法。小鼠模型将使我们能够识别和测试新的疗法。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Microglia deficiency accelerates prion disease but does not enhance prion accumulation in the brain.

DOI：
10.1002/glia.24244
发表时间：
2022-11
期刊：
GLIA
影响因子：
6.2
作者：
Bradford, Barry M.;McGuire, Lynne, I;Hume, David A.;Pridans, Clare;Mabbott, Neil A.
通讯作者：
Mabbott, Neil A.

The evolution of the macrophage-specific enhancer (Fms intronic regulatory element) within the CSF1R locus of vertebrates.

DOI：
10.1038/s41598-017-15999-x
发表时间：
2017-12-07
期刊：
Scientific reports
影响因子：
4.6
作者：
Hume DA;Wollscheid-Lengeling E;Rojo R;Pridans C
通讯作者：
Pridans C

Analysis of the human monocyte-derived macrophage transcriptome and response to lipopolysaccharide provides new insights into genetic aetiology of inflammatory bowel disease.

DOI：
10.1371/journal.pgen.1006641
发表时间：
2017-03
期刊：
PLoS genetics
影响因子：
4.5
作者：
Baillie JK;Arner E;Daub C;De Hoon M;Itoh M;Kawaji H;Lassmann T;Carninci P;Forrest AR;Hayashizaki Y;FANTOM Consortium;Faulkner GJ;Wells CA;Rehli M;Pavli P;Summers KM;Hume DA
通讯作者：
Hume DA

A Transgenic Line That Reports CSF1R Protein Expression Provides a Definitive Marker for the Mouse Mononuclear Phagocyte System