Establishment of Somatic Cell Nuclear Transfer as a Universal Platform for Cloning Marmosets
体细胞核移植作为克隆狨猴通用平台的建立
基本信息
- 批准号:10682479
- 负责人:
- 金额:$ 19.88万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-08-15 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAnatomyAneuploidyAnimalsAntimitotic AgentsBiomedical ResearchBirthBrainCADASILCRISPR/Cas technologyCallithrixCallithrix jacchus jacchusCell NucleusCell fusionCharacteristicsChemicalsChromosomesChronicCloningCognitiveCombined Modality TherapyCommunitiesComplexCrossbreedingCytoplasmCytosineDNADNA MethylationDNA methyltransferase inhibitionDNMT3B geneDNMT3aDeacetylaseDevelopmentDomestic AnimalsEarly Onset Alzheimer DiseaseEmbryoEmbryo CloningEmbryo TransferEmbryonic DevelopmentEpigenetic ProcessFemaleFundingGene ExpressionGene Expression ProfileGene Transfer TechniquesGenerationsGenesGeneticGenetic EngineeringGenetic studyGoalsHistone AcetylationHistonesHumanIn VitroIndividualInfantMeasuresMechanicsMessenger RNAMetabolicMetaphaseMethodsMethyltransferaseMicrovascular DysfunctionModelingMosaicismMusMutationNOTCH3 geneNeurosciences ResearchNuclearOocytesOoplasmPhenotypePhylogenetic AnalysisPhysiologicalPregnancyProceduresProcessProtocols documentationRNAResearchResearch SupportSocial BehaviorSomatic CellStainsSystemTechniquesTechnologyTerm BirthTestingTotipotentTransgenesTransgenic OrganismsTranslational ResearchUltraviolet RaysUnited States National Institutes of HealthVariantWorkassistive reproductive techniqueblastocystcalcium indicatorefficacy evaluationepigenomeexperiencegenome editinghistone demethylasehuman diseasehuman modelimmune functionimprovedinhibitorinterestmosaicnervous system disorderneuropsychiatric disordernonhuman primatenovelnucleasepresenilin-1preservationpreventreproductivesomatic cell nuclear transfertooltranslational neuroscience
项目摘要
PROJECT SUMMARY/ABSTRACT
The common marmoset (Callithrix jacchus) is a New World non-human primate (NHP) with several practical
advantages in biomedical research. Due to their phylogenetic proximity, marmosets are a genetically diverse
NHP species with similar physiological, metabolic, and immunological functions as humans. Marmosets retain
the typical anatomical and functional organization of the human brain. Marmosets have complex cognitive and
social behavior. The above characteristics place marmosets as an ideal NHP model to bridge the gap between
mice and humans for both basic and translational neuroscience. Marmosets reach sexual maturity at circa 18
months and give birth to multiple infants twice a year. Their short gestation period and compatibility with gene
editing techniques make marmosets ideally poised to become the NHP model of choice in studying the genetic
causes of neurological and neuropsychiatric disorders and understanding brain function. We have successfully
generated transgenic marmosets expressing genetically encoded calcium indicators and genetically engineered
marmosets with NOTCH3 mutations that cause the small vessel disease CADASIL. We have also made
marmosets harboring PSEN1 mutations that cause early-onset Alzheimer’s disease. Our gene-edited
marmosets will enable us to investigate the genetic causes of chronic neurological disorders. However, two main
issues hinder the broader availability of genetically engineered marmosets. First, lentiviral-based approaches
suffer from an uncontrollable integration of transgene with variation in copy number, and nuclease-based gene
editing produces embryos with mosaic editing, leading to unpredictable gene expression patterns and variable
phenotype. Second, and most importantly, there are no efficient ways to propagate an individual showing the
interest phenotype. This proposal addresses these shortcomings by developing and optimizing somatic cell
nuclear transfer (SCNT) as a universal platform for cloning marmosets. We want to build on our vast experience
generating genetically modified marmosets to (1) develop and optimize the enucleation procedure in marmoset
somatic cell nuclear transfer and (2) develop and optimize approaches enabling technologies for efficient
epigenetic reprogramming during somatic cell nuclear transfer in the marmoset. These results will establish
optimized marmoset SCNT protocols and unravel a novel enabling universal platform to generate a sizeable
number of cloned marmosets expressing any phenotype of interest. This platform will significantly facilitate the
propagation and sharing of marmoset models for neuroscience and translational research supported by multiple
NIH ICs.
项目总结/文摘
项目成果
期刊论文数量(0)
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Jung Eun Park其他文献
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{{ truncateString('Jung Eun Park', 18)}}的其他基金
Establishment of Somatic Cell Nuclear Transfer as a Universal Platform for Cloning Marmosets
体细胞核移植作为克隆狨猴通用平台的建立
- 批准号:
10510648 - 财政年份:2022
- 资助金额:
$ 19.88万 - 项目类别:
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