CRE MOUSE MODELS TO STUDY AMELOGENESIS
研究釉质形成的 CRE 小鼠模型
基本信息
- 批准号:10674714
- 负责人:
- 金额:$ 41.25万
- 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:2021-08-01 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:AgeAmeloblastsAmelogenesisAnimal ModelAnimalsAnionsCell LineCellsConnexin 43CrossbreedingCystic Fibrosis Transmembrane Conductance RegulatorDentalDental EnamelDepositionDevelopmentDisadvantagedDiseaseEnamel FormationEnamel OrganEnterobacteria phage P1 Cre recombinaseFundingFutureGene ExpressionGenesGrantInvestmentsKeratinKnock-inKnockout MiceKnowledgeLoxP-flanked alleleLungMarylandModelingMultiple Organ FailureMusMutant Strains MiceNational Institute of Dental and Craniofacial ResearchOrganOrganoidsPancreasPathologyPathway interactionsPhaseProteinsPublishingResearchResearch PersonnelResourcesRoleSalivary GlandsSkinTechnologyTestingThe Jackson LaboratoryTissuesTongueTooth structureTracheaameloblastinanimal databronchial epitheliumconditional knockoutgenomic locusin vivo ModelmRNA Expressionmouse Cre recombinasemouse modelmutantnovelpromoterspatiotemporaltool
项目摘要
PROJECT SUMMARY / ABSTRACT
In June of 2017 a group of dental researchers met at the NIDCR to discuss the future of enamel research and
concluded, in a summary statement, that in the field of enamel research, a lack of models to study enamel
formation and disease has hampered recent progress. The group concluded that more appropriate ameloblast-
like cell lines, investment in organoid and chip technology and novel animal models could be used to advance
the field. With respect to animal models, I believe enamel researchers suffer from not having enamel organ-
specific Cre recombinase mutant mouse. For the past 2 decades enamel researchers have used the Krt14-Cre
(keratin 14-Cre recombinase) mutant to study enamel-specific activities by cross breeding with various loxP
mouse lines. The significant disadvantage of using the Krt14-Cre mouse for enamel research is that Krt14 is
expressed in multiple tissues including skin, bronchial epithelia, tongue, trachea, salivary glands, and many
more organs, and because of this many of the developed loxP mouse lines are not appropriate to study
amelogenesis. For example, mRNA expression levels of the anion exchanger protein (Slc4a2/AE2), or the
cystic fibrosis transmembrane conductance regulator (Cftr), increases ~ 6-fold and 3-fold respectively in the
enamel organ during maturation stage (compared to secretory stage), and beyond tooth formation both genes
are widely expressed in lung and pancreas and are critical to their development. Both Slc4a2-null and Cftr-null
mice have severe enamel pathologies. To use the Krt14-Cre mutant mouse to study the role of either AE2fl/fl or
Cftrfl/fl would have significant limitations because these animals would predictably suffer from multiple organ
failures at a young age. I propose to develop two animal models with a knockin of Cre recombinase into the
ameloblastin (Ambn) and odontogenic ameloblast-associated (Odam) gene loci such that Cre expression is
limited to secretory ameloblasts and maturation ameloblasts respectively. The UG3 stage of this grant will be
devoted to the development of these two animal models; Ambn-Cre and Odam-Cre, and the UH3 phase will
validate these two animals as unique in vivo models to study amelogenesis. At the completion of this project
data from these animals will be published, and both lines deposited in an appropriate facility such as the
Mutamt Mouse Resource and Research Centers (MMRRC).
项目摘要/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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Michael Lansdell Paine其他文献
Michael Lansdell Paine的其他文献
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{{ truncateString('Michael Lansdell Paine', 18)}}的其他基金
Doctoral and Post-doctoral Training in Craniofacial Biology
颅面生物学博士和博士后培训
- 批准号:
9518803 - 财政年份:2011
- 资助金额:
$ 41.25万 - 项目类别:
DOCTORAL AND POST-DOCTORAL TRAINING IN CRANIOFACIAL BIOLOGY
颅面生物学博士和博士后培训
- 批准号:
8884400 - 财政年份:2011
- 资助金额:
$ 41.25万 - 项目类别:
DOCTORAL AND POST-DOCTORAL TRAINING IN CRANIOFACIAL BIOLOGY
颅面生物学博士和博士后培训
- 批准号:
8880175 - 财政年份:2011
- 资助金额:
$ 41.25万 - 项目类别:
DOCTORAL AND POST-DOCTORAL TRAINING IN CRANIOFACIAL BIOLOGY
颅面生物学博士和博士后培训
- 批准号:
8269856 - 财政年份:2011
- 资助金额:
$ 41.25万 - 项目类别:
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