Generation and Characterization of a Novel Cell Subpopulation Ablation Model
新型细胞亚群消融模型的生成和表征
基本信息
- 批准号:9932578
- 负责人:
- 金额:$ 21.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-05-21 至 2022-07-31
- 项目状态:已结题
- 来源:
- 关键词:AblationAnimal ModelAnimalsB-LymphocytesBRAIN initiativeBiliaryBindingCD4 Positive T LymphocytesCell CommunicationCell Membrane ProteinsCell physiologyCellsChickensChronicCytomegalovirusDiseaseDisease modelDoseEngineeringEnhancersEpithelialEpithelial CellsEventExperimental Autoimmune EncephalomyelitisFOXP3 geneGenerationsGenetic RecombinationGenetic TranscriptionGoalsHepatocyteHumanHuman Genome ProjectImmuneImmune responseInflammatoryInjectionsInterneuronsLabelLoxP-flanked alleleMediatingMethodologyMethodsModelingMouse StrainsMultiple SclerosisMusNatural regenerationNeuronsParvalbuminsPathogenesisPharmacologyPopulationRecoveryRegulatory T-LymphocyteResourcesRodentRoleSomatostatinStreptococcus intermediusT-LymphocyteT-Lymphocyte SubsetsTarsTestingTimeTissue DifferentiationTissuesTransgenesTransgenic MiceTransgenic Organismsalpha Toxinbeta Actincell injurycell typediphtheria toxin receptorin vivoin vivo regenerationinnovationinstrumentloss of functionmacrophagenovelphenotypic biomarkerrelating to nervous systemresponsetissue regenerationtissue repairtooltranscription factorγδ T cells
项目摘要
Project Summary/Abstract: The primary objective of this application is, for the first time, to generate and
characterize an innovative resource for ablating subsets of cells. This resource will facilitate studying the roles
of different subtypes of cells and their interactions in pathogenesis, tissue repair, and regeneration in vivo. We
propose to advance the resources of cell ablation by generating a novel tool for targeting the subsets of cell
populations that are defined by dual phenotypical markers. Loss-of-function studies using conditional targeted
cell ablation have been widely used to investigate cell function and interaction, tissue repair and differentiation
in vivo though they target only one marker-labelled cell population. Advanced methodologies are changing and
expediting the ways in which we identify and understand immune, neural, and other cell subpopulations. These
cell subpopulations can be labelled by the multiple phenotypical markers. We also anticipate that a growing
spectrum of immune or neural subpopulations will be discovered in The Era of the Brain Initiative and The
Post-Human Genome Project Era. Although current tools are available for ablating a cell population, they
cannot specifically target cell subpopulations because they can only target one maker, not dual-labelled cells.
Therefore, there is a need to develop an instrument that is able to eliminate subsets of cells in animals for loss-
of-function studies. To this end, we propose to generate an intermedilysin (ILY)-mediated cell subpopulation
ablation model. ILY, a toxin secreted by Streptococcus intermedius (SI), exclusively binds to the human cell
membrane protein CD59 (hCD59), but not to CD59 of any other species. Once bound, ILY rapidly and potently
lyses the cells. We recently established a Cre-inducible hCD59 transgenic mouse line (ihCD59) where hCD59
expression only occurs after Cre-mediated recombination. Administration of ILY to various lines of Cre+/-
ihCD59+/- mice resulted in rapid and specific ablation of immune, epithelial or neural cells without off-target
effects. We also tested the ILY/ihCD59-mediated cell ablation method in several disease models to study
immune cell functions, hepatocyte and/or biliary epithelial damage and regeneration, and neural cell damage.
This line (ihCD59) targets only one marker-labelled cell population, and cannot be used for ablating subset cell
population. To further advance this tool towards subset cell ablation, we propose to develop and characterize
CAG (CMV early enhancer/chicken beta actin)-floxP-STOP-floxP-Frt-STOP-Frt (DihCD59) or a double
inducible mouse strain where the transgene (hCD59) expression occurs only following Cre- and Flp-mediated
combinational events. Specifically, we will examine our working hypotheses that 1) hCD59 expression will be
specifically mediated in the targeted subpopulations by Cre- and Flp-mediated combinational events in
DihCD59 or by generating triple (Cre+/Flp+/DihCD59+) transgene positive mice; and that 2) ILY injection to the
triple transgene positive mice will ablate subpopulations of cells for further investigating their functions in vivo.
项目摘要/摘要:该应用程序的主要目标是首次生成和
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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{{ truncateString('Xuebin Qin', 18)}}的其他基金
Role of Complement Activation in Severe COVID-19
补体激活在严重 COVID-19 中的作用
- 批准号:
10765317 - 财政年份:2023
- 资助金额:
$ 21.25万 - 项目类别:
Role of Complement Activation in Severe COVID-19
补体激活在严重 COVID-19 中的作用
- 批准号:
10512248 - 财政年份:2022
- 资助金额:
$ 21.25万 - 项目类别:
Role of Complement Activation in Severe COVID-19
补体激活在严重 COVID-19 中的作用
- 批准号:
10687821 - 财政年份:2022
- 资助金额:
$ 21.25万 - 项目类别:
Development of Therapeutic CD59 inhibitor for treating B-cell malignancies
开发用于治疗 B 细胞恶性肿瘤的治疗性 CD59 抑制剂
- 批准号:
8791256 - 财政年份:2013
- 资助金额:
$ 21.25万 - 项目类别:
Development of Therapeutic CD59 inhibitor for treating B-cell malignancies
开发用于治疗 B 细胞恶性肿瘤的治疗性 CD59 抑制剂
- 批准号:
8725332 - 财政年份:2013
- 资助金额:
$ 21.25万 - 项目类别:
Development of Therapeutic CD59 inhibitor for treating B-cell malignancies
开发用于治疗 B 细胞恶性肿瘤的治疗性 CD59 抑制剂
- 批准号:
8438708 - 财政年份:2013
- 资助金额:
$ 21.25万 - 项目类别:
Development of Therapeutic CD59 inhibitor for treating B-cell malignancies
开发用于治疗 B 细胞恶性肿瘤的治疗性 CD59 抑制剂
- 批准号:
9001317 - 财政年份:2013
- 资助金额:
$ 21.25万 - 项目类别:
Development of Therapeutic CD59 inhibitor for treating B-cell malignancies
开发用于治疗 B 细胞恶性肿瘤的治疗性 CD59 抑制剂
- 批准号:
8607165 - 财政年份:2013
- 资助金额:
$ 21.25万 - 项目类别:
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