# Enamel with overexpressed ameloblastin

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2021 · $361,761

## Abstract

PROJECT SUMMARY/ABSTRACT
Developmental defects of enamel include molar-incisor hypomineralization (MIH). This condition affects the
quality and quantity of enamel and severely disrupts oral functions in children with loss of occlusion, tooth
sensitivity and increased caries susceptibility. Children with MIH have greater needs for dental treatment
throughout their life and often exhibit dental behavioral management problems. MIH is found in many
different populations worldwide with a prevalence ranging from 2.4% to 40.2%. The enamel organ
epithelium is affected by unknown factors resulting in MIH. The pathophysiology of MIH is not understood.
Therapeutic options are limited to conventional therapy with fluoride applications, restorations often with
poor retention and extractions. Enamel formation into the hardest mineral is promoted by enamel matrix
proteins. One of the enamel proteins is ameloblastin (Ambn) accounting for 5% of the enamel proteins. In
hypomineralized enamel, the mineral content does not reach the necessary concentration. Ambn was
identified in hypomineralized enamel of extracted teeth, but it is not clear if it plays a role in the
pathogenesis of MIH. We have developed a mouse model to study the effect of Ambn overexpression in
MIH-like enamel in enamel organ epithelium. When Ambn is overexpressed, the enamel in these mice
displays white, demarcated ‘patches’ that fracture easily from the dentin. The MIH mouse model will serve
to dissect the cellular and molecular events in enamel hypomineralization to identify strategies for the
diagnosis, prevention and therapy of hypomineralized enamel.
We have developed transgenic mice with demarcated, MIH-like lesions in enamel. Our preliminary results
show that the lesions enlarge as the ameloblastin (Ambn) concentration increases. Normally, enamel matrix
is rapidly processed, degraded and internalized by ameloblasts, but when Ambn is overexpressed, the
enamel matrix lingers on and the accumulation of mineral is hampered, manifesting as hypomineralized
enamel. We have developed tools to accurately quantify mineral content and enamel volume with microCT
methods. In a transcriptome analysis of enamel organ epithelium pathways for enamel matrix, enzymatic
degradation, protein trafficking and ion handling were dysregulated. Our overall hypothesis is that
overexpressed ameloblastin influences the mechanisms of enamel formation resulting in MIH lesions in
enamel. In SA1 we will determine the onset of demarcated opacities within the phased formation of enamel in
mice overexpressing Ambn. In SA2, we will determine the biological pathways of endocytosis of enamel
proteins in vivo and in vitro as a consequence of ameloblastin overexpression. In SA3, we will determine if
endocytosis of overexpressed Ambn can be promoted in Ambn mice by increasing the enzymatic activity in
the enamel matrix. For the proposed studies a team of clinician scientists, experts in quantitative imaging,
proteomics and bioinfo...

## Key facts

- **NIH application ID:** 10133047
- **Project number:** 5R01DE026769-05
- **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:** 2021
- **Award amount:** $361,761
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133047

## Citation

> US National Institutes of Health, RePORTER application 10133047, Enamel with overexpressed ameloblastin (5R01DE026769-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10133047. Licensed CC0.

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