CRISPR-mediated engineering and pilot study of mouse mutants of the bitter taste receptor genes

CRISPR介导的小鼠苦味受体基因突变体工程和初步研究

基本信息

  • 批准号:
    10451169
  • 负责人:
  • 金额:
    $ 18.23万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-06-17 至 2025-05-16
  • 项目状态:
    未结题

项目摘要

ABSTRACT: This R03 proposal has been prepared in response to RFA-RM-21-012 entitled “Pilot Projects Investigating Understudied G Protein-Coupled Receptors, Ion Channels, and Protein Kinases.” Our research will focus on human bitter taste receptors (TAS2Rs) in the G protein-coupled receptor family, whose expression is detected in the respiratory system. These receptors have been designated as eligible proteins open for study by NIH’s Illuminating the Druggable Genome (IDG) Program associated with this RFA, and their roles in bitter tastant/TAS2R-agonist-based therapies for asthma need to be elucidated. Asthma is a major public health challenge and the most common chronic disease in the pediatric population. In the United States, over 25 million people, including 8.4% of all children, are currently suffering from asthma with an estimated annual cost of ~$82 billion. At present, the main treatment strategies are based on β2-adrenergic receptor agonists, corticosteroids, and monoclonal antibodies. However, questions remain about the long-term efficacy and safety of these approaches. In addition, there is still no effective treatment for progressive airway remodeling, which plays a critical role in asthma-related deaths. All these factors provide a strong impetus for investigations of bitter tastants/TAS2R agonists for treating asthma because it has been recently shown that these agents have a superior efficacy for asthma treatment in animal models, in which data suggest that these agonists can potentially overcome critical deficiencies associated with current therapeutics such as those related to progressive airway remodeling. The long-term goal of our efforts is to further understand TAS2Rs mechanistically in terms of the physiological, pathological, and therapeutic processes associated with asthma treatment. In this pilot project, we propose to test the hypothesis that bitter taste receptors play an essential role in bitter tastant/TAS2R-agonist- based therapeutic strategies for asthma. Accordingly, we will engineer mouse mutants deficient for Tas2r genes or carrying a single Tas2r gene by using highly efficient CRISPR-based technology. We will also compare the outcomes of bitter tastants/TAS2R-agonist-based treatment of asthma and associated signaling in homozygous mutants and wild-type littermates. These experiments will help us to better understand the molecular mechanisms underlying bitter tastant/TAS2R-agonist-based therapies for asthma. Our study will also reveal if TAS2Rs are essential for the survival of mice. Lastly, the genetic resources developed during this study will be powerful tools for unraveling the physiological, pathological, and therapeutic roles of TAS2Rs related to other medical conditions, such as obesity, diabetes, and preterm labor.
摘要:本R03提案是为响应RFA-RM-21-012“试点项目”而准备的

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)

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Eugene Yu其他文献

Eugene Yu的其他文献

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{{ truncateString('Eugene Yu', 18)}}的其他基金

Generation and analysis of new mouse models to determine novel therapeutic targets for Down syndrome-associated cognitive deficits
生成并分析新的小鼠模型以确定唐氏综合症相关认知缺陷的新治疗靶点
  • 批准号:
    10704099
  • 财政年份:
    2022
  • 资助金额:
    $ 18.23万
  • 项目类别:
Generation and analysis of new mouse models to determine novel therapeutic targets for Down syndrome-associated cognitive deficits
生成并分析新的小鼠模型以确定唐氏综合症相关认知缺陷的新治疗靶点
  • 批准号:
    10518886
  • 财政年份:
    2022
  • 资助金额:
    $ 18.23万
  • 项目类别:
Generation and analysis of new mouse models to determine novel therapeutic targets for Down syndrome-associated cognitive deficits
生成并分析新的小鼠模型以确定唐氏综合症相关认知缺陷的新治疗靶点
  • 批准号:
    10711887
  • 财政年份:
    2022
  • 资助金额:
    $ 18.23万
  • 项目类别:
Mutational analysis to understand the role of CHML in developmental regression
突变分析以了解 CHML 在发育回归中的作用
  • 批准号:
    8877784
  • 财政年份:
    2015
  • 资助金额:
    $ 18.23万
  • 项目类别:
Mutational analysis to understand the role of CHML in developmental regression
突变分析以了解 CHML 在发育回归中的作用
  • 批准号:
    9069905
  • 财政年份:
    2015
  • 资助金额:
    $ 18.23万
  • 项目类别:
Genetic Dissection of Trisomy 21
21 三体的基因剖析
  • 批准号:
    8066350
  • 财政年份:
    2008
  • 资助金额:
    $ 18.23万
  • 项目类别:
Genetic Dissection of Trisomy 21
21 三体的基因剖析
  • 批准号:
    7585303
  • 财政年份:
    2008
  • 资助金额:
    $ 18.23万
  • 项目类别:
Genetic Dissection of Trisomy 21
21 三体的基因剖析
  • 批准号:
    8249053
  • 财政年份:
    2008
  • 资助金额:
    $ 18.23万
  • 项目类别:
Genetic Dissection of Trisomy 21
21 三体的基因剖析
  • 批准号:
    7781344
  • 财政年份:
    2008
  • 资助金额:
    $ 18.23万
  • 项目类别:
Gene Targeting & Transgenic Shared Resource
基因打靶
  • 批准号:
    10641712
  • 财政年份:
    1997
  • 资助金额:
    $ 18.23万
  • 项目类别:
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