# Alternative splicing of ameloblastin in enamel formation

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2022 · $193,750

## Abstract

PROJECT SUMMARY/ABSTRACT
The developmental malformation of dental enamel, known as amelogenesis imperfecta (AI), is a rare
inherited condition. Children and their families affected by AI suffer life-long from a disfigured appearance,
compromised social interactions, psychological suppression, sensitive teeth, increased risk for caries and
bite collapse, inability to masticate. The dental treatment requires full-mouth rehabilitation and frequent, life-
long maintenance. All enamel proteins are known to cause AI. Ameloblastin (Ambn) is the second most
abundant enamel protein. The Ambn gene belongs to the cluster of secreted calcium-binding
phosphoproteins (SCPPs) that originated from the basement membrane gene SPARC. During evolution,
genes for mineralization were selected to specialize for enamel, dentin and bone. Consistent with features
for SCPPs, Ambn is a disordered, phosphorylated, calcium-binding and proline-rich, acidic protein. The
variety of enamel proteins is increased by alternative splicing. Ambn is expressed as full-length and spliced
proteins. The spliced segment is expressed by exon 6 and consist of 15 highly conserved residues,
including an O-glycosylation site and splice site.
Our preliminary data shows that ameloblasts express full-length and spliced Ambn in different
concentrations and different developmental stages. During secretory stage, spliced Ambn is expressed
higher than full-length Ambn. But at maturation stage, the expression of spliced Ambn reduces and full-
length Ambn is expressed higher than spliced. In Ambn null mice, reconstituted with transgenic full-length
Ambn, an enamel layer is present, however the enamel layer is not recovered. This finding suggests that
full-length Ambn is not sufficient for proper enamel and that spliced Ambn may have an important function in
enamel formation. The overall hypothesis is that Ambn splice variants execute distinctly different functions,
depending on the enamel stage. In Specific Aim 1 we will determine the stage-specific functions of full-
length Ambn compared to spliced Ambn in enamel mineralization. In Specific Aim 2 the stage-specific
functions of full-length Ambn vs. spliced Ambn in ameloblasts for cell attachment and basal lamina will be
determined. For the proposed studies a team of clinician scientists, experts in Genome Engineering, Next-
generation sequencing and bioinformatics was assembled for unique interactions and novel approaches.
High resolution imaging and quantification will be applied to study the enamel surface, thickness, density
and hardness. Ameloblasts will be analyzed by stage to understand the pathways for full-length and spliced
Ambn.

## Key facts

- **NIH application ID:** 10361491
- **Project number:** 5R21DE030603-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Yong-Hee Patricia Chun
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $193,750
- **Award type:** 5
- **Project period:** 2021-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10361491

## Citation

> US National Institutes of Health, RePORTER application 10361491, Alternative splicing of ameloblastin in enamel formation (5R21DE030603-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10361491. Licensed CC0.

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