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.

小鼠或人类等哺乳动物基因组中的 DNA 序列包含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（球蛋白），而肝脏不需要这些蛋白质。该项目致力于破译 DNA 内的代码，以确保编码特定产品的基因在正确的时间在正确的位置产生。它专门涉及模型基因 CSF1R 基因，该基因是称为巨噬细胞的大白细胞的产生和功能所必需的。我们唯一能剖析代码各个元素的功能的就是将它们从基因组中删除。在这个项目中，我们将使用小鼠转基因技术来确定如果我们取出控制 CSF1R 产生地点和时间的部分代码，它会发生什么。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，但也有助于修复和再生。它们的功能由 CSF1R 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.

Absence of microglia promotes diverse pathologies and early lethality in Alzheimer's disease mice.

小胶质细胞的缺乏促进了阿尔茨海默氏病小鼠的多种病理和早期致死性。

• DOI: 10.1016/j.celrep.2022.110961
• 发表时间: 2022-06-14
• 期刊: CELL REPORTS
• 影响因子: 8.8
• 作者: Shabestari, Sepideh Kiani;Morabito, Samuel;Danhash, Emma Pascal;McQuade, Amanda;Sanchez, Jessica Ramirez;Miyoshi, Emily;Chadarevian, Jean Paul;Claes, Christel;Coburn, Morgan Alexandra;Hasselmann, Jonathan;Hidalgo, Jorge;Tran, Kayla Nhi;Martini, Alessandra C.;Rothermich, Winston Chang;Pascual, Jesse;Head, Elizabeth;Hume, David A.;Pridans, Clare;Davtyan, Hayk;Swarup, Vivek;Blurton-Jones, Mathew
• 通讯作者: Blurton-Jones, Mathew