HFE: A Genetic Determinant of Olfactory Mn Absorption and Toxicity

HFE:嗅觉锰吸收和毒性的遗传决定因素

基本信息

项目摘要

DESCRIPTION (provided by applicant): Genetic variants of the HFE gene are the leading cause of adult onset hereditary hemochromatosis (HH), the most common Mendelian genetic disease in the North American Caucasian population. The missense variants C282Y and H63D promote increased intestinal absorption and progressive tissue deposition of iron. HH has also been associated with derangements in the metabolism of other divalent metals, and it is thought these effects arise due to malregulation of divalent metal transporter (DMT1). Work in our laboratory has demonstrated that manganese can enter the central nervous system directly across the olfactory epithelium by a mechanism that involves DMT1. We therefore hypothesize that carriers of C282Y and/or H63D HFE alleles may be more susceptible to manganese exposure through the olfactory pathway, and consequently may have impaired olfactory function. Our model further suggests that Hfe-/- knockout mice would have increased 54Mn absorption through the olfactory system and that these animals would be more sensitive to manganese exposures causing impaired olfaction. This pilot project will test the hypothesis that HFE acts as a genetic determinant of olfactory manganese absorption and toxicity. PUBLIC HEALTH RELEVANCE: Genetic variants of the HFE gene are the leading cause of adult onset hereditary hemochromatosis (HH), the most common Mendelian genetic disease in the North American Caucasian population. The missense variants C282Y and H63D promote increased intestinal absorption and progressive tissue deposition of iron. Our hypothesis is that HFE acts as a genetic determinant of olfactory manganese absorption and toxicity. To test this hypothesis, we will study a mouse model of HFE-associated hemochromatosis to test whether absorption of inhaled manganese is altered, and whether HFE therefore promotes a greater susceptibility to damage to olfaction - the sense of smell.
描述(申请人提供):HFE基因的遗传变异是成人遗传性血色素沉着症(HH)的主要原因,HH是北美高加索人群中最常见的孟德尔遗传病。错义变异体C282Y和H63D促进肠道吸收和进行性组织铁沉积。HH也与其他二价金属的代谢紊乱有关,人们认为这些影响是由于二价金属转运蛋白(DMT1)的失调引起的。我们实验室的工作表明,锰可以通过一种涉及DMT1的机制直接穿过嗅觉上皮进入中枢神经系统。因此,我们推测C282Y和/或H63D HFE等位基因携带者可能更容易通过嗅觉途径接触锰,从而可能损害嗅觉功能。我们的模型进一步表明,HFe/-基因敲除小鼠通过嗅觉系统增加了对54MN的吸收,这些动物对导致嗅觉受损的锰暴露更敏感。这个试点项目将测试HFE作为嗅觉锰吸收和毒性的遗传决定因素的假设。 公共卫生相关性:HFE基因的遗传变异是成人遗传性血色素沉着症(HH)的主要原因,HH是北美高加索人群中最常见的孟德尔遗传病。错义变异体C282Y和H63D促进肠道吸收和进行性组织铁沉积。我们的假设是,HFE是嗅觉锰吸收和毒性的遗传决定因素。为了验证这一假设,我们将研究HFE相关性血色病的小鼠模型,以测试吸入的锰的吸收是否发生改变,以及HFe是否因此增加了对嗅觉-嗅觉损伤的敏感性。

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 }}

Marianne Wessling-Resnick其他文献

Marianne Wessling-Resnick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('Marianne Wessling-Resnick', 18)}}的其他基金

Summer Intern Program (SIP) in Environmental Health Sciences
环境健康科学暑期实习生计划(SIP)
  • 批准号:
    8316246
  • 财政年份:
    2011
  • 资助金额:
    $ 16.35万
  • 项目类别:
Summer Intern Program (SIP) in Environmental Health Sciences
环境健康科学暑期实习生计划(SIP)
  • 批准号:
    8216903
  • 财政年份:
    2011
  • 资助金额:
    $ 16.35万
  • 项目类别:
Summer Intern Program (SIP) in Environmental Health Sciences
环境健康科学暑期实习生计划(SIP)
  • 批准号:
    8660697
  • 财政年份:
    2011
  • 资助金额:
    $ 16.35万
  • 项目类别:
Summer Intern Program (SIP) in Environmental Health Sciences
环境健康科学暑期实习生计划(SIP)
  • 批准号:
    8462276
  • 财政年份:
    2011
  • 资助金额:
    $ 16.35万
  • 项目类别:
Summer Intern Program (SIP) in Environmental Health Sciences
环境健康科学暑期实习生计划(SIP)
  • 批准号:
    8843853
  • 财政年份:
    2011
  • 资助金额:
    $ 16.35万
  • 项目类别:
Chemical Genetics of Iron Transport
铁转运的化学遗传学
  • 批准号:
    8013461
  • 财政年份:
    2010
  • 资助金额:
    $ 16.35万
  • 项目类别:
HFE: A Genetic Determinant of Olfactory Mn Absorption and Toxicity
HFE:嗅觉锰吸收和毒性的遗传决定因素
  • 批准号:
    7941943
  • 财政年份:
    2009
  • 资助金额:
    $ 16.35万
  • 项目类别:
Ferristatin: A New Small Molecule Inhibitor of Iron Transport
Ferristatin:一种新的铁转运小分子抑制剂
  • 批准号:
    7831012
  • 财政年份:
    2009
  • 资助金额:
    $ 16.35万
  • 项目类别:
Chemical Genetics of Iron Transport
铁转运的化学遗传学
  • 批准号:
    7898255
  • 财政年份:
    2009
  • 资助金额:
    $ 16.35万
  • 项目类别:
Ferristatin: A New Small Molecule Inhibitor of Iron Transport
Ferristatin:一种新的铁转运小分子抑制剂
  • 批准号:
    7941874
  • 财政年份:
    2009
  • 资助金额:
    $ 16.35万
  • 项目类别:

相似海外基金

Linkage of HIV amino acid variants to protective host alleles at CHD1L and HLA class I loci in an African population
非洲人群中 HIV 氨基酸变异与 CHD1L 和 HLA I 类基因座的保护性宿主等位基因的关联
  • 批准号:
    502556
  • 财政年份:
    2024
  • 资助金额:
    $ 16.35万
  • 项目类别:
Olfactory Epithelium Responses to Human APOE Alleles
嗅觉上皮对人类 APOE 等位基因的反应
  • 批准号:
    10659303
  • 财政年份:
    2023
  • 资助金额:
    $ 16.35万
  • 项目类别:
Deeply analyzing MHC class I-restricted peptide presentation mechanistics across alleles, pathways, and disease coupled with TCR discovery/characterization
深入分析跨等位基因、通路和疾病的 MHC I 类限制性肽呈递机制以及 TCR 发现/表征
  • 批准号:
    10674405
  • 财政年份:
    2023
  • 资助金额:
    $ 16.35万
  • 项目类别:
An off-the-shelf tumor cell vaccine with HLA-matching alleles for the personalized treatment of advanced solid tumors
具有 HLA 匹配等位基因的现成肿瘤细胞疫苗,用于晚期实体瘤的个性化治疗
  • 批准号:
    10758772
  • 财政年份:
    2023
  • 资助金额:
    $ 16.35万
  • 项目类别:
Identifying genetic variants that modify the effect size of ApoE alleles on late-onset Alzheimer's disease risk
识别改变 ApoE 等位基因对迟发性阿尔茨海默病风险影响大小的遗传变异
  • 批准号:
    10676499
  • 财政年份:
    2023
  • 资助金额:
    $ 16.35万
  • 项目类别:
New statistical approaches to mapping the functional impact of HLA alleles in multimodal complex disease datasets
绘制多模式复杂疾病数据集中 HLA 等位基因功能影响的新统计方法
  • 批准号:
    2748611
  • 财政年份:
    2022
  • 资助金额:
    $ 16.35万
  • 项目类别:
    Studentship
Genome and epigenome editing of induced pluripotent stem cells for investigating osteoarthritis risk alleles
诱导多能干细胞的基因组和表观基因组编辑用于研究骨关节炎风险等位基因
  • 批准号:
    10532032
  • 财政年份:
    2022
  • 资助金额:
    $ 16.35万
  • 项目类别:
Recessive lethal alleles linked to seed abortion and their effect on fruit development in blueberries
与种子败育相关的隐性致死等位基因及其对蓝莓果实发育的影响
  • 批准号:
    22K05630
  • 财政年份:
    2022
  • 资助金额:
    $ 16.35万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Investigating the Effect of APOE Alleles on Neuro-Immunity of Human Brain Borders in Normal Aging and Alzheimer's Disease Using Single-Cell Multi-Omics and In Vitro Organoids
使用单细胞多组学和体外类器官研究 APOE 等位基因对正常衰老和阿尔茨海默病中人脑边界神经免疫的影响
  • 批准号:
    10525070
  • 财政年份:
    2022
  • 资助金额:
    $ 16.35万
  • 项目类别:
Leveraging the Evolutionary History to Improve Identification of Trait-Associated Alleles and Risk Stratification Models in Native Hawaiians
利用进化历史来改进夏威夷原住民性状相关等位基因的识别和风险分层模型
  • 批准号:
    10689017
  • 财政年份:
    2022
  • 资助金额:
    $ 16.35万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了