# The molecular mechanism of amelogenin exon4 alternative splicing and its association to amelogenesis imperfecta

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $48,003

## Abstract

PROJECT SUMMARY/ABSTRACT
Enamel, the protective outer layer of our teeth, is crucial for maintaining dental health. A gene called amelogenin
plays a vital role in enamel formation, and it uses a process called alternative splicing to create different versions
of itself for various functions. When mutations occur in the amelogenin gene, it can lead to hereditary enamel
defects known as X-linked Amelogenesis Imperfecta (X-AI). Many mutations that cause hereditary diseases
affect the alternative splicing of the gene, in place of changing the amino acid within the final protein. Instead,
they alter the way the gene is spliced. However, X-AI and its causing mutations in amelogenin have not been
studied in association with alternative splicing until recently. Previous research has shown that a significant
number of X-AI-causing mutations are found in specific parts of the amelogenin gene called exons 4 and 5.
Research has demonstrated that these mutations can disrupt the alternative splicing of exon4 in laboratory
experiments, suggesting a direct link between these mutations, alternative splicing of exon4, and the
development of enamel defects.
However, there is not a full understanding of how this process works in the body or how these mutations impact
enamel formation by the change of alternative splicing in amelogenin. This current study aims to get answers to
these scientific questions by investigating how specific proteins called Ser/Arg rich splicing factors (SRSFs)
influence the splicing of amelogenin exon4. Additionally, the proposal explores how an X-AI-causing mutation
affects splicing patterns and contributes to enamel defects as teeth develop.
By examining these questions, the goal is to better understand the genetic factors behind X-AI and other related
conditions. Patients with X-AI have hypoplastic, hypo mineralized, and/or hypocalcified enamel, resulting in a
reduced quality of life due to discomfort caused by pain, increased chance of pulpal infections, and compromised
appearance. Ultimately, this knowledge could pave the way for improved treatments to enhance the quality of
life for patients affected by enamel defects.

## Key facts

- **NIH application ID:** 11071014
- **Project number:** 1F31DE034641-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Rozana Shemirani
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,003
- **Award type:** 1
- **Project period:** 2024-09-27 → 2027-07-26

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11071014

## Citation

> US National Institutes of Health, RePORTER application 11071014, The molecular mechanism of amelogenin exon4 alternative splicing and its association to amelogenesis imperfecta (1F31DE034641-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11071014. Licensed CC0.

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