CSF1R in homeostasis and immunity

CSF1R 在体内平衡和免疫中的作用

• 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

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.

像小鼠或人类这样的哺乳动物基因组中的DNA序列包含一个代码，该代码指定人体发展和生长的方式。专业类型的细胞仅使用基因组的部分来产生其功能。例如，红细胞必须产生携带氧气所需的蛋白质（球蛋白），其中不需要这些蛋白质。该项目涉及将DNA中的代码解密，以确保在正确的时间在正确的位置生产特定产品代码的基因。它专门处理模型基因CSF1R基因，该基因是称为巨噬细胞的大型白细胞的生产和功能所需的。我们唯一可以剖析代码各个元素的功能的方法是将它们从基因组中删除。在此项目中，我们将使用鼠标转基因技术来确定CSF1R的情况是，我们将删除一个控制该代码的代码。该项目的第二部分应用了生成的工具来确定巨噬细胞的功能。这些细胞在体内每个器官中都发现。它们是人体防御感染的一部分，但也有助于维修和再生。它们的功能由CSF1R基因控制，我们正在开发靶向该基因的疗法。鼠标模型将使我们能够识别和测试新疗法。

项目成果

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

• DOI: 10.4049/jimmunol.2000835
• 发表时间: 2020-12-01
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Grabert, Kathleen;Sehgal, Anuj;Hume, David A.
• 通讯作者: Hume, David A.

Activation of podocyte Notch mediates early Wt1 glomerulopathy.

• DOI: 10.1016/j.kint.2017.11.014
• 发表时间: 2018-04
• 期刊: Kidney international
• 影响因子: 19.6
• 作者: Asfahani RI;Tahoun MM;Miller-Hodges EV;Bellerby J;Virasami AK;Sampson RD;Moulding D;Sebire NJ;Hohenstein P;Scambler PJ;Waters AM
• 通讯作者: Waters AM