Genetic Analysis of Snail Superfamily Genes in Mice
小鼠蜗牛超家族基因的遗传分析
基本信息
- 批准号:8302414
- 负责人:
- 金额:$ 32.11万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1998
- 资助国家:美国
- 起止时间:1998-01-01 至 2014-06-30
- 项目状态:已结题
- 来源:
- 关键词:AllelesAmino Acid MotifsCell ProliferationCellsDNA-Binding ProteinsDevelopmentEmbryoEmbryonic DevelopmentEpithelialEssential Amino AcidsFamilyFundingGene FamilyGene TargetingGenesGeneticGoalsGrantHomozygoteHuman DevelopmentIndividualKnock-in MouseLeftMammalsMediatingMesenchymalMolecular GeneticsMovementMusMuscle DevelopmentMutant Strains MiceMutateMutationNatural regenerationNuclearPhenotypePhosphorylationPhosphotransferasesPhysiologyPlayPost-Translational Protein ProcessingPost-Translational RegulationProcessProtein FamilyProteinsReagentRoleSkeletal MuscleSnailsStagingTestingTranscription Repressor/CorepressorWorkZinc Fingersbeta-Transducin Repeat-Containing Proteinsgastrulationgene repressiongenetic analysisin vivomulticatalytic endopeptidase complexmuscle regenerationmutantpublic health relevanceubiquitin ligase
项目摘要
DESCRIPTION (provided by applicant): Snail superfamily genes encode zinc finger-containing DNA binding proteins that act as transcriptional repressors. This superfamily has two main branches: the Snail family (encoded by the Snai1, 2 and 3 genes) and the Scratch family (the Scrt1 and 2 genes). These proteins are key regulators of the epithelial- mesenchymal transition, and also play roles in cell proliferation, survival and movement. We have performed a comprehensive genetic analysis of the requirements for Snail superfamily genes during embryonic development in mice. Our work during the prior funding periods of this grant established the null phenotype of all of these genes, and demonstrated that the most severe embryonic phenotype is observed in Snai1 mutants. However, many questions remain about the requirements and roles of Snail superfamily genes. In this proposal, both molecular and genetic approaches will be utilized to analyze the roles played by Snail family genes during embryogenesis in mice, and to understand the mechanisms causing the mutant phenotypes. The mutant mouse strains we have already generated, as well as the mutant strains we will construct as part of this proposal, constitute a unique set of reagents that will permit us to finely dissect the roles of Snail family genes during embryonic development. The specific aims of this proposal are: 1) determine targets for transcriptional repression by the SNAI1 protein during early embryogenesis in mice; 2) test the hypothesis that post- translational regulation of SNAI1 protein by the GSK3beta kinase and the betaTrcp ubiquitin ligase are essential for Snai1 function in vivo; 3) test the hypothesis that Snail family genes are important for muscle development, physiology and regeneration by determining the individual roles of the Snai1, Snai2 and Snai3 genes in these processes; 4) assess Snai3 redundancy with Snai2 and Snai1 function during muscle development, physiology and regeneration.
Public Health Relevance: The long-term goal of this proposal is to understand the roles that Snail superfamily genes play during embryonic development in mammals. Snail superfamily genes encode zinc finger-containing DNA binding proteins that act as transcriptional repressors. The studies described in this proposal will further our understanding of the roles played by Snail superfamily genes during mammalian development, and will be relevant to the study of both normal and abnormal human development.
描述(由申请人提供):蜗牛超家族基因编码含有锌指的DNA结合蛋白,其充当转录抑制子。该超家族有两个主要分支:Snail 家族(由 Snai1、2 和 3 基因编码)和 Scratch 家族(Scrt1 和 2 基因)。这些蛋白质是上皮-间质转化的关键调节因子,也在细胞增殖、存活和运动中发挥作用。我们对小鼠胚胎发育过程中对 Snail 超家族基因的需求进行了全面的遗传分析。我们在本次资助之前的资助期间的工作确定了所有这些基因的无效表型,并证明在 Snai1 突变体中观察到最严重的胚胎表型。然而,关于蜗牛超家族基因的要求和作用仍然存在许多问题。在该提案中,将利用分子和遗传学方法来分析 Snail 家族基因在小鼠胚胎发生过程中所发挥的作用,并了解导致突变表型的机制。我们已经产生的突变小鼠品系,以及我们将作为该提案的一部分构建的突变品系,构成了一套独特的试剂,使我们能够精细剖析蜗牛家族基因在胚胎发育过程中的作用。该提案的具体目标是:1)确定小鼠早期胚胎发生过程中SNAI1蛋白转录抑制的靶点; 2) 检验以下假设:GSK3beta 激酶和 betaTrcp 泛素连接酶对 SNAI1 蛋白的翻译后调节对于 Snai1 体内功能至关重要; 3) 通过确定 Snai1、Snai2 和 Snai3 基因在这些过程中的各自作用,检验 Snail 家族基因对于肌肉发育、生理和再生很重要的假设; 4) 评估肌肉发育、生理和再生过程中 Snai3 与 Snai2 和 Snai1 功能的冗余。
公共健康相关性:该提案的长期目标是了解蜗牛超家族基因在哺乳动物胚胎发育过程中发挥的作用。蜗牛超家族基因编码含有锌指的 DNA 结合蛋白,充当转录抑制因子。本提案中描述的研究将进一步了解蜗牛超家族基因在哺乳动物发育过程中所发挥的作用,并将与正常和异常人类发育的研究相关。
项目成果
期刊论文数量(31)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Absence of a major role for the snai1 and snai3 genes in regulating skeletal muscle regeneration in mice.
snai1 和 snai3 基因在调节小鼠骨骼肌再生中缺乏主要作用。
- DOI:10.1371/currents.md.e495b27ee347fd3870a8316d4786fc17
- 发表时间:2013
- 期刊:
- 影响因子:0
- 作者:Norton,ChristineR;Chen,Ying;Han,XiangHua;Bradley,CaraK;Krebs,LukeT;Yoon,JeongKyo;Gridley,Thomas
- 通讯作者:Gridley,Thomas
Stromal SNAI2 Is Required for ERBB2 Breast Cancer Progression.
- DOI:10.1158/0008-5472.can-20-0278
- 发表时间:2020-12-01
- 期刊:
- 影响因子:11.2
- 作者:Blanco-Gómez A;Hontecillas-Prieto L;Corchado-Cobos R;García-Sancha N;Salvador N;Castellanos-Martín A;Sáez-Freire MDM;Mendiburu-Eliçabe M;Alonso-López D;De Las Rivas J;Lorente M;García-Casas A;Del Carmen S;Abad-Hernández MDM;Cruz-Hernández JJ;Rodríguez-Sánchez CA;Claros-Ampuero J;García-Cenador B;García-Criado J;Orimo A;Gridley T;Pérez-Losada J;Castillo-Lluva S
- 通讯作者:Castillo-Lluva S
Snail1 controls TGF-β responsiveness and differentiation of mesenchymal stem cells.
- DOI:10.1038/onc.2012.342
- 发表时间:2013-07-11
- 期刊:
- 影响因子:8
- 作者:Batlle, R.;Alba-Castellon, L.;Loubat-Casanovas, J.;Armenteros, E.;Franci, C.;Stanisavljevic, J.;Barderas, R.;Martin-Caballero, J.;Bonilla, F.;Baulida, J.;Casal, J. I.;Gridley, T.;Garcia de Herreros, A.
- 通讯作者:Garcia de Herreros, A.
The Notch-regulated ankyrin repeat protein is required for proper anterior-posterior somite patterning in mice.
- DOI:10.1002/dvg.20813
- 发表时间:2012-04
- 期刊:
- 影响因子:1.5
- 作者:Krebs, Luke T.;Bradley, Cara K.;Norton, Christine R.;Xu, Jingxia;Oram, Kathleen F.;Starling, Christa;Deftos, Michael L.;Bevan, Michael J.;Gridley, Thomas
- 通讯作者:Gridley, Thomas
The snail family gene snai3 is not essential for embryogenesis in mice.
- DOI:10.1371/journal.pone.0065344
- 发表时间:2013
- 期刊:
- 影响因子:3.7
- 作者:Bradley CK;Norton CR;Chen Y;Han X;Booth CJ;Yoon JK;Krebs LT;Gridley T
- 通讯作者:Gridley T
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THOMAS HOOKER GRIDLEY其他文献
THOMAS HOOKER GRIDLEY的其他文献
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{{ truncateString('THOMAS HOOKER GRIDLEY', 18)}}的其他基金
9: NOTCH SIGNALING AND SKELETAL MUSCLE FUNCTION
9:Notch 信号传导和骨骼肌功能
- 批准号:
8360272 - 财政年份:2011
- 资助金额:
$ 32.11万 - 项目类别:
SCREENING FOR NOTCH AND SNAIL MUTANTS, AND ROLES OF IGFBP-2
NOTCH 和 SNAIL 突变体的筛选以及 IGFBP-2 的作用
- 批准号:
8360273 - 财政年份:2011
- 资助金额:
$ 32.11万 - 项目类别:
Modifiers of a Mouse Model of Alagille Syndrome
阿拉吉尔综合征小鼠模型的改良剂
- 批准号:
6999791 - 财政年份:2003
- 资助金额:
$ 32.11万 - 项目类别:
Modifiers of a Mouse Model of Alagille Syndrome
阿拉吉尔综合征小鼠模型的改良剂
- 批准号:
7324851 - 财政年份:2003
- 资助金额:
$ 32.11万 - 项目类别:
Modifiers of a Mouse Model of Alagille Syndrome
阿拉吉尔综合征小鼠模型的改良剂
- 批准号:
6836063 - 财政年份:2003
- 资助金额:
$ 32.11万 - 项目类别:
Modifiers of a Mouse Model of Alagille Syndrome
阿拉吉尔综合征小鼠模型的改良剂
- 批准号:
7152951 - 财政年份:2003
- 资助金额:
$ 32.11万 - 项目类别:
Modifiers of a Mouse Model of Alagille Syndrome
阿拉吉尔综合征小鼠模型的改良剂
- 批准号:
6723515 - 财政年份:2003
- 资助金额:
$ 32.11万 - 项目类别:
ANIMAL MODELS FOR SAETHRE CHOTZEN SYNDROME
SAETHRE CHOTZEN 综合征的动物模型
- 批准号:
6346116 - 财政年份:1999
- 资助金额:
$ 32.11万 - 项目类别:
ANIMAL MODELS FOR SAETHRE CHOTZEN SYNDROME
SAETHRE CHOTZEN 综合征的动物模型
- 批准号:
6481901 - 财政年份:1999
- 资助金额:
$ 32.11万 - 项目类别:
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