Genetic basis for gravity receptor dysfunction in mice

小鼠重力感受器功能障碍的遗传基础

基本信息

  • 批准号:
    7850286
  • 负责人:
  • 金额:
    $ 17.56万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-07-17 至 2011-11-30
  • 项目状态:
    已结题

项目摘要

3.4% of the US adult population, or 6.2 million individuals, experience chronic dizziness and/or imbalance. While the prevalence of these conditions is greater among older adults, balance problems can occur at any age. The cause of dizziness/imbalance often remains unknown and treatment may often be unsuccessful. Could there be a genetic basis for dizziness/imbalance in some of these individuals? While much is being learned about the genetics of deafness, relatively little is known about the role genes may play in vestibular dysfunction (i.e., vestibular impairment occurring in the absence of significant hearing loss). Not all genetic mutations produce both cochlear and vestibular abnormalities. Otoconia-deficient mice (e.g., het, tit) are examples of selective vestibular impairment due to genetic mutations. Preliminary data have identified inbred mouse strains with early onset, profound macular deficits and normal hearing. Our hypothesis is that genetic mutations exist, which produce selective, hereditary vestibular impairment. Furthermore, we hypothesize that the selective vestibular impairment is due to deficits other than otoconial loss. The proposed research will test these hypotheses. Specific Aim 1will identify inbred strains that exhibit gravity receptor impairment by 3 months of age. We will record linear vestibular evoked potentials (VsEPs) and auditory brainstem responses (ABR) in age matched animals to determine the functional status of the macular and auditory organs, respectively. Specific aim 2 will characterize gravity receptor function in relation to age in those strains identified with vestibular impairment in specific aim 1. VsEPs will be collected at several ages to describe the time course and nature of the macular deficit. ABRs will be collected to confirm the absence of significant hearing impairment. Specific aim 3 will examine end organ and primary afferent anatomy to identify putative structural correlates for the functional deficits evaluated in specific aim 2. We will examine morphological features of hair cell stereocilia and bundles, the numbers and distributions of hair cell types, key structures at synapses and the relative number, size and distribution of afferent neurons. Specific aim 4 will map loci that contribute to gravity receptor dysfunction using genome-wide linkage analyses of two inbred strain backcrosses. This research will extend our understanding of vestibular ontogeny and vestibular dysfunction. In addition, we will identify loci for hereditary vestibular impairment providing the basis for identifying specific genes affecting the vestibular system and, potentially, genetic homologs for human vestibular disease. This work may lead to better diagnosis and treatment of vestibular impairment.
3.4%的美国成年人口,即620万人,经历着慢性头晕和/或失衡。 虽然这些疾病在老年人中的患病率更高,但平衡问题在任何 年龄。头晕/不平衡的原因通常仍不清楚,治疗可能经常不成功。 这些人中的一些人头晕/不平衡可能有遗传基础吗?虽然很多事情都是 了解了耳聋的遗传学,对基因在前庭中可能扮演的角色知之甚少 功能障碍(即,在没有明显听力损失的情况下发生的前庭损害)。不全是遗传的 突变会导致耳蜗病和前庭畸形。耳石缺陷小鼠(如het、山雀)是 由于基因突变而导致的选择性前庭损害的例子。初步数据表明,近亲交配 发病早、黄斑深度缺陷、听力正常的小鼠品系。我们的假设是基因 突变是存在的,它会导致选择性遗传性前庭损伤。此外,我们假设 选择性前庭功能障碍是由于耳锥缺失以外的其他原因造成的。拟议的研究将 检验这些假设。特定目标1将通过以下方式鉴定表现出重力感受器损伤的近交系 3个月大。我们将记录线性前庭诱发电位(VsEP)和听性脑干 年龄匹配动物的ABR反应(ABR)以确定黄斑和听觉的功能状态 分别是器官。特定目标2将描述与年龄相关的重力感受器功能 在特定目标中鉴定出前庭功能障碍的菌株1.将在几个年龄段收集VsEP 描述黄斑缺损症的时间进程和性质。将收集ABR以确认不存在 严重的听力障碍。特指3将检查末梢器官和初级传入解剖 确定在特定目标中评估的功能缺陷的假定结构相关性2。我们将检查 毛细胞立体纤毛和毛束的形态特征,毛细胞类型的数量和分布, 突触的关键结构以及传入神经元的相对数量、大小和分布。具体目标4 将使用两个基因的全基因组连锁分析来定位导致重力感受器功能障碍的基因座 近交系回交。这项研究将扩大我们对前庭个体发育和前庭的理解 功能障碍。此外,我们还将确定遗传性前庭功能障碍的基因座,为 确定影响前庭系统的特定基因,并可能识别人类的遗传同源物 前庭疾病。这项工作可能导致更好的前庭功能障碍的诊断和治疗。

项目成果

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SHERRI M JONES其他文献

SHERRI M JONES的其他文献

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{{ truncateString('SHERRI M JONES', 18)}}的其他基金

Genetic basis for gravity receptor dysfunction in mice
小鼠重力感受器功能障碍的遗传基础
  • 批准号:
    7320642
  • 财政年份:
    2005
  • 资助金额:
    $ 17.56万
  • 项目类别:
Genetic basis for gravity receptor dysfunction in mice
小鼠重力感受器功能障碍的遗传基础
  • 批准号:
    7048133
  • 财政年份:
    2005
  • 资助金额:
    $ 17.56万
  • 项目类别:
Genetic basis for gravity receptor dysfunction in mice
小鼠重力感受器功能障碍的遗传基础
  • 批准号:
    7157563
  • 财政年份:
    2005
  • 资助金额:
    $ 17.56万
  • 项目类别:
Genetic basis for gravity receptor dysfunction in mice
小鼠重力感受器功能障碍的遗传基础
  • 批准号:
    7727924
  • 财政年份:
    2005
  • 资助金额:
    $ 17.56万
  • 项目类别:
Genetic basis for gravity receptor dysfunction in mice
小鼠重力感受器功能障碍的遗传基础
  • 批准号:
    7534030
  • 财政年份:
    2005
  • 资助金额:
    $ 17.56万
  • 项目类别:
SCREENING VESTIBULAR FUNCTION USING EVOKED POTENTIALS
使用诱发电位筛查前庭功能
  • 批准号:
    6074863
  • 财政年份:
    1999
  • 资助金额:
    $ 17.56万
  • 项目类别:
SCREENING VESTIBULAR FUNCTION USING EVOKED POTENTIALS
使用诱发电位筛查前庭功能
  • 批准号:
    6379553
  • 财政年份:
    1999
  • 资助金额:
    $ 17.56万
  • 项目类别:
SCREENING VESTIBULAR FUNCTION USING EVOKED POTENTIALS
使用诱发电位筛查前庭功能
  • 批准号:
    6176010
  • 财政年份:
    1999
  • 资助金额:
    $ 17.56万
  • 项目类别:
SCREENING VESTIBULAR FUNCTION USING EVOKED POTENTIALS
使用诱发电位筛查前庭功能
  • 批准号:
    6780612
  • 财政年份:
    1999
  • 资助金额:
    $ 17.56万
  • 项目类别:
FUNCTION OF THE MACULA LAGENA
黄斑的功能
  • 批准号:
    2128010
  • 财政年份:
    1995
  • 资助金额:
    $ 17.56万
  • 项目类别:

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