# CRE MOUSE MODELS TO STUDY AMELOGENESIS

> **NIH NIH UH3** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2022 · $408,375

## Abstract

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).

## Key facts

- **NIH application ID:** 10460289
- **Project number:** 5UH3DE028850-04
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Michael Lansdell Paine
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $408,375
- **Award type:** 5
- **Project period:** 2021-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10460289

## Citation

> US National Institutes of Health, RePORTER application 10460289, CRE MOUSE MODELS TO STUDY AMELOGENESIS (5UH3DE028850-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10460289. Licensed CC0.

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