MATH 1 AND CNS AND PNS DEVELOPMENT
数学 1 以及 CNS 和 PNS 发展
基本信息
- 批准号:6391726
- 负责人:
- 金额:$ 2.58万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2001
- 资助国家:美国
- 起止时间:2001-09-01 至
- 项目状态:未结题
- 来源:
- 关键词:alleles brain stem cell differentiation central nervous system developmental neurobiology gene expression gene targeting genetic mapping genetic markers immunocytochemistry inbreeding laboratory mouse neurogenesis neurogenetics neuropathology peripheral nervous system phenotype protein structure function respiration regulatory center respiratory function respiratory insufficiency /failure rhombencephalon
项目摘要
In Drosophila, atonal encodes a basic helix-loop-helix (bHLH) protein essential for the development of chordotonal organs (sensory organs for proprioception, balance and audition). The mouse atonal homolog 1 (Math1) is expressed in the hindbrain, dorsal neural tube, inner ear, Merkel cells, and joints. Gene targeting in mice revealed that Mah1 is essential for the genesis of cerebellar granule neurons and inner ear hair cells. Furthermore, Math1 null nice die shortly after birth because of inability to breathe. To investigate the influence of Math1 on the differentiation of neurons involved in respiratory control, we will assess the neurophysiological integrity of the respiratory circuitry in Math1 null embryos, fate-map embryonic brainstem neurons that express Math1 null newborns die quickly, we will also target atonal into the Math1 locus to ascertain which facets of the phenotype can be rescued. Complete rescue will identify the bHLH domain as the mediator of Math1 function; partial rescue will indicate that other portions of the protein are necessary in the mammal. These data will allow future analysis of molecular interactions in the development of the brainstem, cerebellum and inner ear hair cells, with ramifications for understanding cerebellar anomalies, deafness, balance disorders, and neonatal breathing dysfunctions.
在果蝇中,无调编码一种基本的螺旋-环-螺旋(bHLH)蛋白,这种蛋白对弦音器官(本体感觉、平衡和听觉的感觉器官)的发育至关重要。小鼠无调同源物1(Math 1)在后脑、背神经管、内耳、默克尔细胞和关节中表达。小鼠基因打靶实验表明,Mah 1对小脑颗粒神经元和内耳毛细胞的发生至关重要。此外,Math 1 null nice在出生后不久就因为无法呼吸而死亡。为了研究Math 1对参与呼吸控制的神经元分化的影响,我们将评估Math 1无效胚胎中呼吸回路的神经生理学完整性,表达Math 1无效新生儿的胚胎脑干神经元快速死亡,我们还将无调靶向Math 1基因座以确定表型的哪些方面可以被拯救。完全拯救将确定bHLH结构域作为Math 1功能的介体;部分拯救将表明该蛋白的其他部分在哺乳动物中是必需的。这些数据将允许未来分析脑干,小脑和内耳毛细胞发育中的分子相互作用,并对理解小脑异常,耳聋,平衡障碍和新生儿呼吸功能障碍产生影响。
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)
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Vincent Yat-Chung Wang其他文献
Vincent Yat-Chung Wang的其他文献
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