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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：
Michael Lansdell Paine
金额：
$ 41.25万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
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：
https://reporter.nih.gov/project-details/10674714
关键词：
Age Ameloblasts Amelogenesis Animal Model Animals Anions Cell Line Cells Connexin 43 Crossbreeding Cystic Fibrosis Transmembrane Conductance Regulator Dental Dental Enamel Deposition Development Disadvantaged Disease Enamel Formation Enamel Organ Enterobacteria phage P1 Cre recombinase Funding Future Gene Expression Genes Grant Investments Keratin Knock-in Knockout Mice Knowledge LoxP-flanked allele Lung Maryland Modeling Multiple Organ Failure Mus Mutant Strains Mice National Institute of Dental and Craniofacial Research Organ Organoids Pancreas Pathology Pathway interactions Phase Proteins Publishing Research Research Personnel Resources Role Salivary Glands Skin Technology Testing The Jackson Laboratory Tissues Tongue Tooth structure Trachea ameloblastin animal data bronchial epithelium conditional knockout genomic locus in vivo Model mRNA Expression mouse Cre recombinase mouse model mutant novel promoter spatiotemporal tool

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