# Function of albinism gene oca2 in non-melanocyte cell development

> **NIH NIH R03** · WASHINGTON STATE UNIVERSITY · 2021 · $76,500

## Abstract

Project summary
Loss of function mutations in the oculocutaneous albinism 2 (oca2) gene not only lead to
defects in black pigment (melanin) synthesis important for skin color, but also increase the
chances of developing “side” or “pleiotropic” effects. Some examples of pleiotropic effects
include deficiencies in sensory or neural system development, as well as embryonic death
depending on the identity of the mutated gene. Although pleiotropic effects are commonly
observed in humans with hypopigmentation disorders like Waardenburg Syndrome and
albinism, the underlying mechanisms are poorly understood primarily due to low sample size.
Because pigment cells are easily viewed through transparent skin and eggs can be collected in
high numbers year round, we propose to use zebrafish silver cells to better understand how
pleiotropic effects arise. When oca2 is mutated, zebrafish larvae continue to make the correct
number of black pigment cells, melanocytes, but melanin synthesis is severely decreased.
Conversely, silver pigment cells do not express oca2, but are increased in number at stages
following specification from neural crest. Using oca2 mutant iridophores as a model, we will
address the following R03 specific aims: 1) Determine the iridophore developmental stages
impacted by oca2 function. With aim 1 experiments, we will retest the role of oca2 in iridophore
specification and examine iridophore development at multiple, additional stages including
proliferation, differentiation and survival – all cellular events that could impact cell number; 2)
Determine if oca2 directly or indirectly regulates iridophore number. Using our unique collection
of melanocyte mutants, we will determine if oca2 directly (cell-autonomously) or indirectly (non-
cell autonomously) regulates iridophore development. In additional experiments, we will
conduct pilot [bulk and single cell RNA-Seq] analysis to determine if these methods can
provide insight into oca2’s autonomous versus non-autonomous role during iridophore
development. Specifically, these RNA-seq data will be analyzed to determine whether changes
in the expression of intrinsic or extrinsic genes important for iridophore development occur with
oca2 loss of function. Once these experiments are complete, we will have a characterized
model for testing oca2 function in pleiotropic effects and a substantial amount of preliminary
data for formulating hypotheses appropriate for R01 level research aimed at elucidating
mechanistic connections between melanocytes/melanin and hearing/visual/skin system
development in humans.

## Key facts

- **NIH application ID:** 10303820
- **Project number:** 1R03HD103609-01A1
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** Cynthia D COOPER
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $76,500
- **Award type:** 1
- **Project period:** 2021-07-14 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10303820

## Citation

> US National Institutes of Health, RePORTER application 10303820, Function of albinism gene oca2 in non-melanocyte cell development (1R03HD103609-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10303820. Licensed CC0.

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