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Vestibular function analysis in mice

小鼠前庭功能分析

基本信息

批准号：
8242224
负责人：
Tomoko Makishima
金额：
$ 19.85万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8242224
关键词：
Acceleration Address Adopted Aging Animal Model Animals Area Auditory Award Behavior Behavioral Bilateral Cloning Control Groups Coupled Data Development Diagnostic Disease Disease model Dizziness Elderly Environment Equilibrium Event Financial compensation Frequencies Functional disorder Genes Genetic Genome engineering Goals Hearing Histology Human Impairment Intervention K-Series Research Career Programs Knowledge Laboratories Labyrinth Maintenance Measurement Measures Methods Molecular Molecular Biology Molecular Genetics Motion Mus Mutant Strains Mice Organ Orthologous Gene Otolaryngology Otology Performance Peripheral Phenotype Physiology Posture Prevention Process Reflex action Research Role Rotation Scientist Semicircular canal structure Sensitivity and Specificity Sensory Staging Stimulus Symptoms System Test Result Testing Time Vestibular Function Tests Vestibular loss Vision Visual Wild Type Mouse age effect age related career caspase-3 cell type equilibration disorder expectation experience inner ear diseases innovation interest labyrinthectomy loss of function malformation mouse model mutant mouse model neurobehavioral oculomotor otoconia prevent relating to nervous system response skills

项目摘要

DESCRIPTION (provided by applicant): This career development award will help fill in the knowledge and skills in vestibular research, an area in which the PI lacks, and is critical for the goal to become an inner ear expert. The goal during the award period is to correlate the molecular events in the inner ear to the neurobehavioral phenotype of the auditory and vestibular system. The long-term objective is to determine the environment leading to vestibular dysfunction in mutant mice, and to apply the information to treat/prevent vestibular dysfunction in humans. The mouse has become a popular animal model for inner ear research due to the feasibility of engineering the genome, and due to cloning of mouse orthologs of genes important for the development and maintenance of hearing and balance in humans. Unlike the auditory function, the vestibular function in most of these mutant mice are not characterized due to technical difficulty of vestibular function analysis in mice. A large knowledge gap exists in determining the mechanisms leading to the vestibular phenotype. In order to characterize the unique molecular environment in each of these mutant mice with vestibular dysfunction, it is important to first accurately assess the type of vestibular dysfunction using a combination of different tests that are adopted for mice. We will perform vestibulo-ocular response (VOR) tests to assess semicircular canal function, as well as utilize a combination of tilt/rocking paradigm in VOR and pseudo-off vertical axis stimulus tests to assess otolith organ function. We will compare the results with mice with unilateral and bilateral vestibular dysfunction to assess the compensation process. We will characterize the inner ear function in caspase-3 deficient mice, a mutant mouse model for vestibular dysfunction. When the proposed studies have been completed, it is our expectation that we will be able to compare basic results of vestibular dysfunction in mice and in human. PUBLIC HEALTH RELEVANCE: The information obtained from the proposed study can be used as basic standards in measurements of vestibular function in other mice models for human vestibular disorders. The similarities and differences in vestibular test results between humans and mice can be utilized to develop prevention and/or treatment methods for vestibular dysfunction and balance disorders.

描述（由申请人提供）：此职业发展奖将有助于填补PI缺乏的前庭研究领域的知识和技能，对成为内耳专家的目标至关重要。奖励期间的目标是将内耳中的分子事件与听觉和前庭系统的神经行为表型联系起来。长期目标是确定导致突变小鼠前庭功能障碍的环境，并应用这些信息来治疗/预防人类前庭功能障碍。由于基因组工程的可行性，以及克隆小鼠同源基因对人类听力和平衡的发展和维持很重要，小鼠已成为内耳研究的流行动物模型。与听觉功能不同，由于对小鼠前庭功能分析的技术困难，大多数突变小鼠的前庭功能无法表征。在确定导致前庭表型的机制方面存在很大的知识差距。为了表征每种具有前庭功能障碍的突变小鼠的独特分子环境，重要的是首先使用小鼠采用的不同测试组合来准确评估前庭功能障碍的类型。我们将进行前庭-眼反应（VOR）试验来评估半规管功能，并利用VOR的倾斜/摇晃模式和伪垂直轴刺激试验的组合来评估耳石器官功能。我们将比较单侧和双侧前庭功能障碍小鼠的结果，以评估代偿过程。我们将描述caspase-3缺陷小鼠的内耳功能，这是一种前庭功能障碍的突变小鼠模型。当提出的研究完成后，我们期望能够比较小鼠和人类前庭功能障碍的基本结果。