The Mutant Mouse Resource and Research Center at The Jackson Laboratory
杰克逊实验室突变小鼠资源和研究中心
基本信息
- 批准号:10400428
- 负责人:
- 金额:$ 49.19万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-01 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:2019-nCoVACE2AcuteAnimal ModelAnimalsBasic ScienceBiologyBiomedical ResearchBody Weight decreasedBrainBreedingCOVID-19COVID-19 patientCatalogsClinicalCommunitiesComplementary DNAComplexDNA Sequence AlterationDNA sequencingDataDiseaseDisease OutcomeDisease ProgressionDoseEngineeringEnsureFeedbackFutureGenesGeneticGenetic EngineeringGenetic TranscriptionGenomeHeterogeneityHistologicHumanInbred StrainInbreedingInfectionInstitutesKeratinKnock-inKnock-in MouseLaboratory miceLeadershipLightLinkMeasuresModelingMonitorMusMutant Strains MiceOutcomePatternPhasePhenotypePhysiologyPredispositionProcessPublishingReproducibilityResearchResearch PersonnelResourcesRoleSARS-CoV-2 infectionSamplingScientistShipsSpecificitySpeedTechnologyTestingThe Jackson LaboratoryTissue SampleTissuesTransgenic MiceVariantViralbasebiobankcohortdrug testingexperiencegenetic approachgenetic varianthuman modelinfection ratemodel developmentmouse geneticsmouse modelparent grantpatient responsepre-clinicalpromoterreceptorresearch and developmentresponsetooltranscriptometranscriptome sequencingtranscriptomicsviral genomics
项目摘要
Abstract
To date, most of the research using mouse models for COVID-19 has been done using a transgenic
mouse model expressing high levels of the human ACE2gene driven by the Keratin-18(K18) promoter.
While this model has been extremely useful, it has some notable limitations: disease progression is
rapid and invariably fatal within one week, with an uncharacteristically high infection rate in the brain.
These features restrict its use to study the biology related to the acute phase of the infection, leaving a
gap in models that more accurately reflect the expression patterns and levels of the ACE2 receptor, and
that extend the disease course beyond the acute phase of infection.
We will employ a refined genetic strategy utilizing a recently published knock-in model of the human
ACE2 cDNA into the mouse Ace2 locus. By crossing these hACE2 knock-in mice with inbred
Collaborative Cross (CC) founder strains, and by characterizing the response of resulting humanized
F1 progeny to live SARS-CoV-2 infection through an established partnership with researchers at the
Trudeau Institute, we will test the hypothesis that clinical variation in COVID-19 patient response can
be more accurately modelled and phenotypically characterized in mice with naturally regulated ACE2
expression on variable genetic backgrounds.
Consistent with the aims of MMRRC parent grant to identify and distribute mouse models to the
biomedical community, this proposal aims to rapidly provide the research community with an urgently
needed resource for linking the variability in COVID-19 disease outcome with underlying host genetic
features, and for developing precision models for post infection sequelae.
摘要
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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Cathleen M Lutz其他文献
Cathleen M Lutz的其他文献
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{{ truncateString('Cathleen M Lutz', 18)}}的其他基金
Project 4: Therapeutic Gene Editing for Rett Syndrome
项目 4:雷特综合征的治疗性基因编辑
- 批准号:
10668770 - 财政年份:2023
- 资助金额:
$ 49.19万 - 项目类别:
Interrogation of Neurological Pathologies Associated with Mutations in Kif1a
与 Kif1a 突变相关的神经病理学研究
- 批准号:
10728701 - 财政年份:2023
- 资助金额:
$ 49.19万 - 项目类别:
The Jackson Laboratory Center for Precision Genetics
杰克逊精密遗传学实验室中心
- 批准号:
10469581 - 财政年份:2020
- 资助金额:
$ 49.19万 - 项目类别:
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