Mouse models for study of the NLRP1 and CARD8 inflammasomes

用于研究 NLRP1 和 CARD8 炎性体的小鼠模型

基本信息

  • 批准号:
    10493370
  • 负责人:
  • 金额:
    $ 19.44万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-09-22 至 2024-08-31
  • 项目状态:
    已结题

项目摘要

ABSTRACT Inflammasomes are multiprotein complexes that function as cytosolic sensors. As such, they respond to compromise and alteration of cellular metabolism and integrity resulting from both endogenous and exogenous “danger-associated stimuli”. Conversely, aberrant and chronic inflammasome activation can contribute to autoinflammatory diseases. Assembly of the inflammasome complex results in autoactivation of caspases, maturation of IL-1β and IL-18, and often pyroptotic cell death. While there is a downstream commonality in the events following inflammasome activation, the specificity of the response is dependent on germline-encoded pattern recognition receptors triggered by the specific danger-associated stimuli. Many of the cellular sensors such as NLRP3 belong to the NLR gene family, and much of our understanding of the contribution of individual inflammasomes to the innate immune responses to a plethora of environmental challenges has been gleaned from the study of mouse lines lacking various NLRs. In contrast, there is limited information regarding the contribution to immune responses of two inflammasomes that are the focus of this proposal: NLRP1 and CARD8. A major factor in the lack of information on these two related inflammasomes is the limited availability of animal models to evaluate the function of the human inflammasome. Major differences in the functions of human and mouse NLRP1 are suggested by species differences in NLRP1 protein structure and expression pattern. In the case of CARD8, in vivo validation of the functions tentatively assigned to this protein have been impossible in mice/rodents because the gene is absent in these species. Thus, the study of this inflammasome has depended almost entirely on in vitro and ex vivo studies using human cell lines and tissue. We propose to address this gap in our knowledge by utilizing syntenic replacement to generate novel mouse lines expressing human NLRP1 and CARD8.
摘要 炎性小体是一种多蛋白复合体,起到胞液感受器的作用。因此,他们会对 内源性和外源性导致的细胞代谢和完整性的折衷和改变 “危险相关的刺激”。相反,异常和慢性炎症性小体激活可导致 自身炎症性疾病。炎症体复合体的组装导致半胱氨酸天冬氨酸酶的自动激活, IL-1β和IL-18成熟,常有嗜热性细胞死亡。虽然在下游有一个共同点,但 炎性小体激活后的事件,反应的特异性取决于生殖线编码 由特定危险相关刺激触发的模式识别受体。许多细胞传感器 如NLRP3属于NLR基因家族,我们对个体的贡献了解很多 已收集到针对过多环境挑战的先天免疫反应的炎症体 来自对缺乏各种NLR的小鼠品系的研究。相比之下,关于 这两个炎症体对免疫反应的贡献是这一提议的重点:NLRP1和NLRP1 CARD8。缺乏关于这两个相关炎症体的信息的一个主要因素是可获得性有限 以评估人类炎症小体的功能。在功能上的主要差异 人类和小鼠NLRP1的蛋白质结构和表达存在物种差异 图案。在CARD8的情况下,已经对初步分配给该蛋白质的功能进行了体内验证 在老鼠/啮齿动物中是不可能的,因为这种基因在这些物种中缺失。因此,对这个炎症体的研究 几乎完全依赖于使用人类细胞系和组织进行的体外和体外研究。我们建议 通过利用共线替换来产生新的鼠线表达来填补我们知识中的这一缺口 人类NLRP1和CARD8。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Beverly H Koller其他文献

The hippocratic finger points the blame at PGE2
希波克拉底的手指指向 PGE2 应受责备。
  • DOI:
    10.1038/ng0608-691
  • 发表时间:
    2008-06-01
  • 期刊:
  • 影响因子:
    29.000
  • 作者:
    Kenneth G Coggins;Thomas M Coffman;Beverly H Koller
  • 通讯作者:
    Beverly H Koller

Beverly H Koller的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Beverly H Koller', 18)}}的其他基金

Role and Mitigation of Inflammasomes and Inflammation During COVID-19
COVID-19 期间炎症小体和炎症的作用和缓解
  • 批准号:
    10521963
  • 财政年份:
    2022
  • 资助金额:
    $ 19.44万
  • 项目类别:
Modeling the contribution of coronavirus cellular tropism to viral pathogenesis
模拟冠状病毒细胞向性对病毒发病机制的贡献
  • 批准号:
    10583101
  • 财政年份:
    2022
  • 资助金额:
    $ 19.44万
  • 项目类别:
Role and Mitigation of Inflammasomes and Inflammation During COVID-19
COVID-19 期间炎症小体和炎症的作用和缓解
  • 批准号:
    10666572
  • 财政年份:
    2022
  • 资助金额:
    $ 19.44万
  • 项目类别:
Humanized mouse models for arsenic toxicology
砷毒理学的人源化小鼠模型
  • 批准号:
    10653131
  • 财政年份:
    2021
  • 资助金额:
    $ 19.44万
  • 项目类别:
Humanized mouse models for arsenic toxicology
砷毒理学的人源化小鼠模型
  • 批准号:
    10470377
  • 财政年份:
    2021
  • 资助金额:
    $ 19.44万
  • 项目类别:
Role and Mitigation of Inflammasomes and Inflammation During COVID-19
COVID-19 期间炎症小体和炎症的作用和缓解
  • 批准号:
    10470451
  • 财政年份:
    2021
  • 资助金额:
    $ 19.44万
  • 项目类别:
Mouse models for study of the NLRP1 and CARD8 inflammasomes
用于研究 NLRP1 和 CARD8 炎性体的小鼠模型
  • 批准号:
    10354472
  • 财政年份:
    2021
  • 资助金额:
    $ 19.44万
  • 项目类别:
Humanized mouse models for arsenic toxicology
砷毒理学的人源化小鼠模型
  • 批准号:
    10312344
  • 财政年份:
    2021
  • 资助金额:
    $ 19.44万
  • 项目类别:
Genetically humanized mice for modeling human Fc-receptor interaction during influenza infection
用于模拟流感感染期间人类 Fc 受体相互作用的基因人源化小鼠
  • 批准号:
    10117188
  • 财政年份:
    2020
  • 资助金额:
    $ 19.44万
  • 项目类别:
Assembly of disease-relevant pathways in the mouse
小鼠疾病相关通路的组装
  • 批准号:
    8638644
  • 财政年份:
    2014
  • 资助金额:
    $ 19.44万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 19.44万
  • 项目类别:
    Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 19.44万
  • 项目类别:
    Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 19.44万
  • 项目类别:
    Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 19.44万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 19.44万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 19.44万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 19.44万
  • 项目类别:
    EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 19.44万
  • 项目类别:
    Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 19.44万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 19.44万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了