# Enamel with overexpressed ameloblastin

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2024 · $349,370

## Abstract

PROJECT SUMMARY/ABSTRACT
Molar-Incisor Hypomineralization (MIH) is a highly prevalent in children all around the globe affecting their
primary and permanent teeth. The affected enamel has chalky to yellow lesions that are demarcated and
less mineralized causing increased caries susceptibility, enamel breakout, esthetic concerns and sensitive
teeth. While the treatment and management of these lesions are challenging, the pathophysiology of MIH is
not known, hampering the development of a precise, targeted therapy. A striking feature of MIH is the
demarcation of defects, such that affected and unaffected enamel are located adjacently, with abrupt
changes in mineral density. This feature is in stark contrast to fluorosis which is characterized by diffuse
hypomineralization. Ameloblastin is one of the essential enamel proteins required for proper enamel
formation. In the absence of ameloblastin enamel is hypoplastic, known as amelogenesis imperfecta. When
ameloblastin is expressed too much, the enamel displays demarcated, hypomineralized lesions in mice.
The pathoetiology of MIH is unknown. Exposure to environmental toxicants are currently discussed. The
enamel of MIH teeth is characterized by an imbalance of enamel proteins and enzymes degrading the
m atrix.
The hypothesis of this research is that ameloblastin overexpression causes demarcated and
hypomineralized lesions through enzymatic imbalance. The proposed Aims will define the pathways of
demarcated enamel hypomineralization caused by Ambn overexpression and insufficient enzyme. In SA1
we will determine if demarcated, hypomineralized lesions are caused by insufficient enzyme relative to
ameloblastin overexpression. In SA2, we will determine the transcriptome and transcriptional regulation of
Ambn and overexpressed Ambn in ameloblasts using cultured primary enamel organ epithelium, termed
‘ameloblastoids’. In SA3, findings from the mouse model will be translated into a minimally invasive MIH
treatment protocol addressing conditioning and infiltrating the porous, hypomineralized enamel. Ultimately,
this project will bridge the gap in MIH treatment by translating basic and preclinical research into clinical
research.

## Key facts

- **NIH application ID:** 10920355
- **Project number:** 5R01DE026769-07
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Yong-Hee Patricia Chun
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $349,370
- **Award type:** 5
- **Project period:** 2023-09-05 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10920355

## Citation

> US National Institutes of Health, RePORTER application 10920355, Enamel with overexpressed ameloblastin (5R01DE026769-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10920355. Licensed CC0.

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