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
- 来源:
- 关键词:AddressAdrenal Cortex HormonesAdrenergic AgonistsAgonistAllelesAllergensAnimal ModelAreaAsthmaBiologicalBiological ProcessBronchodilationCRISPR/Cas technologyCause of DeathCell ProliferationCellsCessation of lifeChildChildhoodChromosomesChronic DiseaseClinicalClinical ManagementClustered Regularly Interspaced Short Palindromic RepeatsCodeCost of IllnessDataDiabetes MellitusDiseaseDrug TargetingEngineeringFamilyFamily memberFinancial compensationFundingG-Protein-Coupled ReceptorsGene ClusterGene FamilyGenesGenomeGoalsHealth Care CostsHumanIndividualInflammatory ResponseInvestigationIon Channel ProteinMediatingMedicalMolecularMonoclonal AntibodiesMusMuscarinic Acetylcholine ReceptorMuscle relaxation phaseMutant Strains MiceObesityObstructive Lung DiseasesOral cavityOrthologous GeneOutcomePathologicPathologic ProcessesPersonsPharmacologyPhenotypePhysiologicalPilot ProjectsPlayPopulationPremature LaborProcessProtein KinaseProteinsPublic HealthQuinineReceptor GeneRefractoryRegulationResearchResourcesRespiratory SystemRoleSafetySignal TransductionSmooth Muscle MyocytesTaste BudsTechnologyTestingTherapeuticTherapeutic EffectTherapeutic StudiesTreatment outcomeUnited StatesUnited States National Institutes of Healthairway remodelingallergic airway inflammationantagonistbasebeta-2 Adrenergic Receptorsbody systemcostdesensitizationdruggable targeteffective therapyexperimental studygenetic resourcegenetic testinginsightmast cellmouse modelmutantnovelpreventprogramsreceptorrespiratory smooth muscleresponsesuccesstooltreatment strategy
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:














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