A Novel Locus in the Regulation of Human Water Balance
人体水平衡调节的新途径
基本信息
- 批准号:10047697
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-10-01 至 2022-09-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAffinityAlgorithmsAllelesAnimal ModelAnimalsBindingBiologicalBiological AssayBlood Chemical AnalysisBody WaterBrainCell Culture TechniquesCell LineCell VolumesCellsCerebral EdemaCessation of lifeClinicalCodeCognitionComaConfusionConsensusCultured CellsDNADNA BindingDataDiseaseElectrolytesElementsEngineeringEnhancersEquilibriumExcretory functionExhibitsFamilyGene ExpressionGenesGeneticHeart failureHeritabilityHumanHyponatremiaImpairmentIn VitroInappropriate ADH SyndromeIndividualInheritedInternationalIntronsInvestigationIslets of LangerhansKidney FailureKnock-outLeadLethargiesLiver FailureLocationMeasuresMinorModelingMolecularMusMutationOsmolalitiesOsmoregulationPatientsPhenotypePhysiologicalPlasmaPlayPopulationPopulation GeneticsPredictive FactorPredisposing FactorProteinsQuantitative Trait LociRegulationReporter GenesRiskRoleSeizuresSeriesSignal TransductionSiteSodiumSodium BicarbonateSodium-Bicarbonate SymportersStressSyndromeTestingTissuesTransgenic MiceTubeUnited States Department of Veterans AffairsVariantWaterantidiuresisbasecohortdesigngene productgenetic variantgenome wide association studymembermetagenomemouse modelnovelprogramsresponsesensorsolutetraittranscription factor
项目摘要
Hyponatremia, a relative excess of total body water, is the most frequently encountered electrolyte
abnormality. Although some instances are readily attributed to heart, liver, or kidney failure, many are
unexplained. Water excess causes confusion, lethargy, seizures, and death. Even mild hyponatremia
causes reversible deficits in coordination and cognition.
The applicant's preliminary data show that the plasma sodium concentration is highly individual (i.e.,
relatively constant in any one individual) and is heritable. In a meta-genome-wide association study for
common gene variants that influence water balance, the applicant and co-workers identified variants in
a gene not previously suspected of playing a role in whole-body water balance, but exhibiting extremely
high biological plausibility. The lead variant affects an intronic enhancer within the gene. Remarkably, a
second association locus codes for the transcription factor predicted to bind this enhancer. Therefore,
the overarching objective of this proposal is to demonstrate the centrality of this enhancer region, this
gene variant, and this gene to systemic osmoregulation using a combination of in vitro and whole-
animal models.
In Aim 1, the functional significance (i.e., osmotic responsiveness) of the enhancer region and allele-
specific effects will be probed through reporter gene and DNA binding assays. In Aim 2, the effect of
downregulating this gene upon osmotic phenotype will be tested in cultured cells natively expressing
the protein. In Aim 3, transgenic mouse models will be used to test the importance of this gene to
systemic water balance under basal conditions, and in response to physiological maneuvers designed
to perturb water balance.
低钠血症是一种相对过量的身体水分,是最常见的电解质
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 }}
DAVID M COHEN其他文献
DAVID M COHEN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('DAVID M COHEN', 18)}}的其他基金
A Novel Locus in the Regulation of Human Water Balance
人体水平衡调节的新途径
- 批准号:
10474258 - 财政年份:2017
- 资助金额:
-- - 项目类别:
相似海外基金
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
- 批准号:
2301846 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
- 批准号:
23K16076 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Early-Career Scientists