# Dissecting out differential molecular phenotypes across Lysine(K) AcetylTransferase mutations in mouse development

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $191,244

## Abstract

PROJECT ABSTRACT
Epigenetic factors are genes that encode proteins that can affect spatial organization of DNA and the
accessibility of genetic regions to transcriptional machinery, thereby regulating cell-type specific transcription.
Pathogenic mutations in established epigenes are highly enriched in children with pediatric syndromic disorders,
often with symptoms that affect multiple organ systems, such as the brain, heart, gastrointestinal tract, bone, eye
and kidneys. The associated symptoms of intellectual disability, developmental delays, autism, diarrhea and
congenital heart defects vary in severity between individuals. The onset of these syndromes during early
childhood suggest that many of these epigenetic factors are critical to early developmental processes and cell-
fate transitions. Despite our improved diagnostic ability with exome sequencing, the mechanistic link between
epigenetic factor mutations and the direct mechanisms by which they disrupt mammalian developmental
processes remains unknown. Histone acetyltransferases (HATs) are genes that acetylate lysine (K) residues
and represent a common mechanism for controlling DNA accessibility to the transcriptional machinery. Here, we
study protein-truncating variants in two HATs: Lysine (K), Acetyl transferase 6A and 6B (KAT6A and KAT6B),
which cause Arboleda-Tham Syndrome (ARTHS) and Genitopatellar Syndrome (GPS) or Say-Barber-Biesecker-
Young Syndrome (SBBYS), respectively. Our goal is to develop and validate transgenic mouse models harboring
patient-specific mutations in these genes to establish the differential roles of these epigenetic factors on cell
specification during development driving the distinct syndromes.

## Key facts

- **NIH application ID:** 10891666
- **Project number:** 5R21OD035421-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Valerie A Arboleda
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $191,244
- **Award type:** 5
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10891666

## Citation

> US National Institutes of Health, RePORTER application 10891666, Dissecting out differential molecular phenotypes across Lysine(K) AcetylTransferase mutations in mouse development (5R21OD035421-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10891666. Licensed CC0.

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