权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Molecular profile of cranial motor neurons

颅运动神经元的分子概况

基本信息

批准号：
6835225
负责人：
DONGXIAN ZHANG
金额：
$ 19.1万
依托单位：
SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-12-12 至 2005-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6835225
关键词：
amyotrophic lateral sclerosis cranial nerves gene expression profiling in situ hybridization laboratory mouse laboratory rat laser capture microdissection messenger RNA microarray technology motor neurons neural degeneration polymerase chain reaction superoxide dismutase

项目摘要

DESCRIPTION (provided by applicant): We are interested primarily in the specific susceptibility of motor neurons to Amyotrophic Lateral Sclerosis (ALS). ALS results in selective degeneration of motor neurons despite that factors contributing to ALS are also present in other CNS neurons that are generally resistant to ALS. Even among motor neurons there are differing degrees of susceptibility to ALS. For example, cranial nerve nuclei Ill, IV, and VI in the brainstem are relatively resistant to ALS, while facial nucleus motor neurons inevitably succumb to degeneration. Since only subsets of neurons degenerate in ALS, we hypothesize that there may be specific features of motor neurons that confer susceptibility. Identification and characterization of unique molecules that either diminish or enhance a motor neuron's vulnerability to degeneration are critical to understanding and eventually treating motor neuron diseases. Along these lines, knowledge of the gene and protein expression profiles of a specific motor neuron group is critical to understanding their susceptibility to the effects of motor neuron disease. Therefore, we propose to identify genes uniquely expressed in cranial motor neurons by gene profiling using microarray and real-time PCR methods in normal and Cu/Zn superoxide dismutase (SOD1) mutant mice, a mouse model of ALS. Such a study will allow us to understand the molecular architecture and function specific to motor neurons and also will establish a screening system for studying gene expression alterations in motor neuron diseases. The Specific Aims of this study are outlined below. Specific Aim 1. To identify motor neuron-specific gene expression by gene profiling. We will undertake cell sorting and laser capture microdissection to isolate mRNAs expressed in motor neurons of cranial motor nuclei. The genes expressed specifically in motor neurons will be identified and compared in normal and SOD1 mutant mice by DNA microarray and real-time PCR. Specific Aim 2. To define differential expression of motor neuron-specific genes in cranial motor nuclei of normal and SOD1 mutant mice. We will determine by in situ hybridization the expression patterns of motor neuron-specific genes in cranial motor nuclei identified in Specific Aim 1. Differential expression levels of these genes will be further quantified by real-time PCR.

描述（由申请人提供）：我们主要感兴趣的是运动神经元对肌萎缩侧索硬化症（ALS）的特异性易感性。ALS导致运动神经元的选择性变性，尽管导致ALS的因素也存在于通常对ALS有抗性的其他CNS神经元中。即使在运动神经元中，也存在对ALS的不同程度的易感性。例如，脑干中的颅神经核III、IV和VI对ALS相对有抵抗力，而面神经核运动神经元不可避免地屈服于变性。由于只有神经元亚群在ALS中退化，我们假设可能有特定的运动神经元特征赋予易感性。识别和表征减少或增强运动神经元对变性的脆弱性的独特分子对于理解和最终治疗运动神经元疾病至关重要。沿着这些路线，一个特定的运动神经元组的基因和蛋白质表达谱的知识是至关重要的，以了解他们的易感性运动神经元疾病的影响。因此，我们建议，以确定独特的基因表达在颅运动神经元的基因分析，使用微阵列和实时PCR方法在正常和铜/锌超氧化物歧化酶（SOD 1）突变小鼠，ALS的小鼠模型。这样的研究将使我们能够了解运动神经元的分子结构和功能，也将建立一个筛选系统，研究基因表达改变的运动神经元疾病。本研究的具体目的概述如下。具体目标1.通过基因表达谱分析确定运动神经元特异性基因表达。我们将进行细胞分选和激光捕获显微切割，以分离表达在颅运动核运动神经元的mRNA。将通过DNA微阵列和实时PCR技术，在正常和SOD1突变小鼠中鉴定和比较运动神经元中特异性表达的基因。具体目标2。目的：明确运动神经元特异性基因在正常和SOD1突变小鼠颅运动核团中的差异表达。我们将通过原位杂交确定运动神经元特异性基因在特定目标1中确定的颅运动核中的表达模式。这些基因的差异表达水平将通过实时PCR进一步定量。