Analysis of surviving math1-null hair cells in the inner ear of chimeric mice
嵌合小鼠内耳中存活的 math1-null 毛细胞的分析
基本信息
- 批准号:7901248
- 负责人:
- 金额:$ 8.14万
- 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:2009-08-14 至 2010-07-31
- 项目状态:已结题
- 来源:
- 关键词:ActinsAddressAgeBreedingCell CommunicationCell Differentiation processCellsChimera organismChimerismCochleaComplementCuesDataDevelopmentEmbryoEnvironmentFounder GenerationGalactosidaseGenerationsGenesGoalsGreen Fluorescent ProteinsHair CellsImageryIn SituIn VitroIndividualKnockout MiceLabelLabyrinthLasersLifeLiving WillsLongevityMaintenanceMediatingMicroscopyMolecularMolecular ProfilingMusNull LymphocytesPathway interactionsPlayProcessProteinsRNAReporterRoleStagingSystemTestingTimeTissuesTransgenic MiceWild Type Mousebasecell typecongenital deafnessdeafnessimmunocytochemistryin vivoinsightmRNA Expressionmembermutantmyosin VInotch proteinpostnatalpromoterprotein expressionresearch studytissue processingtranscription factor
项目摘要
DESCRIPTION (provided by applicant): Math1, a transcription factor, is one of the critical genes for the formation of hair cells (HC) in the inner ear. The importance of Math1 was first shown in Math1 knockout mice which lack HCs (Bermingham et. al., 1999) leading to the hypothesis that Math1 was essential and sufficient for the formation of HCs. However, our recent study demonstrated that Math1- null HCs are able to be generated and to properly differentiate in the Math1-null chimeric mice, in which Math1-null cells are intermingled with wild-type cells (Du et. al., 2007). The presence of Math1-null cells within the chimeric inner ear provides evidence both that 1) wild-type cells can rescue Math1-null HCs in the chimeric environment, and 2) that given the correct external cues, cells that lack Math1 remain able to differentiate as hair cells (Du et. al., 2007). These unique cells can now be used to further explore the role of Math1 in HC development by more extensively characterizing their long-term potential as well as identifying molecular candidates that may mediate this rescue. A limitation of the previous study was that the system used to mark the genotypically mutant HCs, ss-galactosidase (ss-gal) from the mutant construct, was decreasing in expression and thus examination of mutant cells could be followed only up to postnatal days 4.5. Moreover, the tissue processing needed for ss-gal visualization compromised the integrity of the RNA. In the present proposal, these limitations will be circumvented by several chimeric combinations including the use of Math1-null mice that constitutively express green fluorescent protein and the use of other marker systems in the wild-type mice (including ROSA26 transgenic mice). Specific Aim 1 will begin to examine the long-term potential of these cells by testing the hypothesis that these HCs survive a normal lifespan and appear morphologically normal at all ages. Thus, the inner ears of chimeric mice will be examined at a range of ages using immunocytochemistry for HC markers. While the mechanism of this rescue is currently unknown, we hypothesize that at the time of differentiation of HCs, wild-type cells are able to activate downstream or parallel molecular pathways, allowing rescue of genotypically mutant HCs. Specific Aim 2 will compare the expression profiles of several molecules (e.g. Delta1, Bdnf) in chimeric Math1- null cells with those from the controls to assess whether these are molecular candidates for mediating this rescue. This data will provide information about the role of Math1 in the expression of these molecules as well as provide insight into the role of other molecules in the rescue of the genotypically Math1-null cells in the chimeric environment. One of the potential means to cure congenital deafness or deafness that occurs later in life is through the generation of new hair cells in the inner ear and Math1 is one of the candidate molecules that has shown promise in being able to generate new hair cells. This proposal will provide insight into how Math1 functions in the generation of hair cells.
描述(由申请人提供):Math 1是一种转录因子,是内耳毛细胞(HC)形成的关键基因之一。Math 1的重要性首先在缺乏HC的Math 1敲除小鼠中显示(Berlovet.例如,1999年)导致的假设,数学1是必不可少的,足以形成HC。然而,我们最近的研究表明,Math 1- null HC能够在Math 1-null嵌合小鼠中产生并适当分化,其中Math 1-null细胞与野生型细胞混合(Du et.例如,2007年)。嵌合内耳内Math 1-null细胞的存在提供了以下两方面的证据:1)野生型细胞可以在嵌合环境中拯救Math 1-null HC,以及2)给予正确的外部提示,缺乏Math 1的细胞仍然能够分化为毛细胞(Du et.例如,2007年)。这些独特的细胞现在可用于进一步探索Math 1在HC发育中的作用,方法是更广泛地表征其长期潜力,并鉴定可能介导这种拯救的分子候选物。以前的研究的一个局限性是,用于标记基因型突变HC的系统,突变体构建体的β-半乳糖苷酶(β-gal)的表达下降,因此只能跟踪到出生后4.5天的突变细胞的检查。此外,ss-gal可视化所需的组织处理损害了RNA的完整性。在本发明中,这些限制将通过几种嵌合组合来规避,包括使用组成型表达绿色荧光蛋白的Math 1-null小鼠和在野生型小鼠(包括ROSA 26转基因小鼠)中使用其他标记系统。具体目标1将开始检验这些细胞的长期潜能,方法是检验这些HC在正常寿命内存活并在所有年龄段表现出形态正常的假设。因此,嵌合小鼠的内耳将在一定年龄范围内使用HC标志物的免疫细胞化学进行检查。虽然这种拯救的机制目前尚不清楚,但我们假设在HC分化时,野生型细胞能够激活下游或平行的分子途径,从而拯救基因型突变的HC。具体目标2将比较嵌合Math 1- null细胞中几种分子(例如Delta 1,Bdnf)的表达谱与对照细胞中的表达谱,以评估这些分子是否是介导这种拯救的候选分子。这些数据将提供有关Math 1在这些分子表达中的作用的信息,并提供对其他分子在嵌合环境中拯救基因型Math 1-null细胞中的作用的了解。治疗先天性耳聋或以后发生的耳聋的潜在方法之一是通过在内耳中产生新的毛细胞,Math 1是能够产生新毛细胞的候选分子之一。该提案将深入了解Math 1在毛细胞生成中的功能。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
KRISTIN M HAMRE其他文献
KRISTIN M HAMRE的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('KRISTIN M HAMRE', 18)}}的其他基金
Gender and Genetic effects on sleep:wake parameters following ethanol exposure
性别和遗传对睡眠的影响:乙醇暴露后的唤醒参数
- 批准号:
8119666 - 财政年份:2010
- 资助金额:
$ 8.14万 - 项目类别:
Gender and Genetic effects on sleep:wake parameters following ethanol exposure
性别和遗传对睡眠的影响:乙醇暴露后的唤醒参数
- 批准号:
7991274 - 财政年份:2010
- 资助金额:
$ 8.14万 - 项目类别:
Analysis of surviving math1-null hair cells in the inner ear of chimeric mice
嵌合小鼠内耳中存活的 math1-null 毛细胞的分析
- 批准号:
7725823 - 财政年份:2008
- 资助金额:
$ 8.14万 - 项目类别:
Analysis of surviving math1-null hair cells in the inner ear of chimeric mice
嵌合小鼠内耳中存活的 math1-null 毛细胞的分析
- 批准号:
7588335 - 财政年份:2008
- 资助金额:
$ 8.14万 - 项目类别:
Mapping Cerebellar Development in Time and Space
绘制小脑发育的时间和空间图
- 批准号:
8068050 - 财政年份:2005
- 资助金额:
$ 8.14万 - 项目类别:
Mapping Cerebellar Development in Time and Space
绘制小脑发育的时间和空间图
- 批准号:
7449641 - 财政年份:2005
- 资助金额:
$ 8.14万 - 项目类别:
Mapping Cerebellar Development in Time and Space
绘制小脑发育的时间和空间图
- 批准号:
7635905 - 财政年份:2005
- 资助金额:
$ 8.14万 - 项目类别:
Mapping Cerebellar Development in Time and Space
绘制小脑发育的时间和空间图
- 批准号:
7255420 - 财政年份:2005
- 资助金额:
$ 8.14万 - 项目类别:
INIA: Chimeric Analysis of Alcohol & Stress Interactions
INIA:酒精的嵌合分析
- 批准号:
6622583 - 财政年份:2002
- 资助金额:
$ 8.14万 - 项目类别:
INIA: Chimeric Analysis of Alcohol & Stress Interactions
INIA:酒精的嵌合分析
- 批准号:
6694113 - 财政年份:2002
- 资助金额:
$ 8.14万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 8.14万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 8.14万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 8.14万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 8.14万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 8.14万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 8.14万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 8.14万 - 项目类别:
EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 8.14万 - 项目类别:
Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 8.14万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 8.14万 - 项目类别:
Research Grant