Role of TrpmI3 in Sensory Cells

TrpmI3 在感觉细胞中的作用

• 批准号: 8004933
• 负责人: Natalie N Remis
• 金额: $ 3.34万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8004933
• 关键词: Ablation; Accessory Olfactory Bulbs; Action Potentials; Affect; Afferent Neurons; Aggressive behavior; Anatomy; Antibodies; Auditory; Auditory Brainstem Responses; Behavior; Behavioral; Behavioral Assay; Biological Assay; Caenorhabditis elegans; Cell Death; Cells; Chemicals; Defect; Deformity; Development; Diagnosis; Drosophila melanogaster; Dyes; Ear; Embryo; Esthesia; Family member; Female; Genes; Goals; Hair Cells; Hearing; Impairment; Ion Channel; Knockout Mice; Labyrinth; Lead; Learning; Light; Maintenance; Mammals; Measures; Mechanics; Mediating; Modality; Molecular; Mus; Mutate; Optics; Organ; Partner in relationship; Pattern; Pheromone; Physiological; Play; Point Mutation; Pregnancy; Prevention; Process; Proteins; Receptor Cell; Research; Role; Scanning Electron Microscopy; Sensory; Sensory Disorders; Sensory Hair; Sensory Process; Sensory Receptors; Signal Transduction; Staging; Stereocilium; Structure; Tamoxifen; Taste Perception; Testing; Tissues; Transgenic Mice; Transgenic Organisms; Vesicle; Vestibular Hair Cells; Visual; Work; base; cellular microvillus; cellular transduction; deafness; gain of function; gain of function mutation; hearing impairment; implantation; knockout gene; memory recognition; mutant; neuronal cell body; olfactory marker protein; postnatal; promoter; public health relevance; receptor; recombinase; response; uptake; vomeronasal organ

DESCRIPTION (provided by applicant): TRP channels of various metazoans mediate nearly every sensory modality, including thermal, mechanical, visual and chemical (i.e., taste and vomeronasal). A gain-of-function mutation in the Trpml3 gene causes deafness and other defects in the Varitint-waddler mouse. We have found that Trpml3 is expressed in hair cells of the inner ear as well as in another type of primary sensory neuron. The long-term goal of this research is to determine what the function of Trpml3 is in two types of sensory receptor cells. I propose to determine the function of Trpml3 in these sensory cells using a Trpml3 conditional knockout mouse I have made. I will generate mice in which Trpml3 is conditionally deleted in hair cells (before and after their development), as well as mice in which Trpml3 is deleted in other sensory neurons. I will then determine the effects of Trpml3 deletion on the anatomy of hair cells and sensory neurons (using light and scanning electron microscopy) and on their sensory function (using behavioral as well as physiological tests such as Auditory Brainstem Responses). Theses studies aim to elucidate Trpml3's function within sensory cells of the inner ear and in other primary sensory neurons. PUBLIC HEALTH RELEVANCE: Currently there is still much to be learned about the auditory process in the ear and in other sensory organs. When the molecular components and their functions in sensory processing is more thoroughly understood it will lead to a better understanding of all how all the mechanisms work together in order to mediate sensory transduction and elicit appropriate responses, which will lead to better prevention, diagnosis and treatment in sensory disorders.

描述（由申请人提供）：各种后生动物的TRP通道几乎介导了几乎所有感觉方式，包括热，机械，视觉和化学（即味觉和呕吐）。 TRPML3基因的功能收益突变会导致变异 - waddler小鼠的耳聋和其他缺陷。我们发现TRPML3在内耳的毛细胞以及另一种类型的原发性神经元中表达。这项研究的长期目标是确定TRPML3在两种类型的感觉受体细胞中的功能。我建议使用我制作的有条件敲除鼠标来确定这些感觉细胞中TRPML3的功能。我将生成在毛细胞中有条件删除TRPML3的小鼠（在发育之前和之后），以及在其他感觉神经元中删除TRPML3的小鼠。然后，我将确定TRPML3缺失对毛细胞和感觉神经元解剖学的影响（使用光和扫描电子显微镜）及其感觉功能（使用行为和生理测试，例如听觉脑干反应）。这些研究旨在阐明内耳和其他原发性神经元中感觉细胞中TRPML3的功能。 公共卫生相关性：目前，关于耳朵和其他感官器官中的听觉过程还有很多值得了解的知识。当分子成分及其在感觉过程中的功能得到更彻底的了解时，它将更好地理解所有机制如何共同工作以介导感觉转导并引起适当的反应，这将导致更好的预防，诊断和治疗感官障碍。