# Functional Analysis of Schizophrenia-Associated Genes

> **NIH NIH R00** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $249,000

## Abstract

PROJECT SUMMARY/ABSTRACT
The goal of this project is to investigate the functions of schizophrenia-associated genes using zebrafish as a
model system. Large-scale genome-wide association studies have begun to uncover numerous candidate
genes linked to schizophrenia. Yet it remains unclear how these genes function and how they contribute to the
underlying molecular, cellular, developmental and behavioral processes disrupted in the disorder. Recent
technological breakthroughs in zebrafish – targeted genome editing, whole-brain activity imaging, brain atlas
registration, behavioral profiling – combined with the ease of studying large numbers of animals make it an
ideal system for analyzing psychiatric disease genes. Preliminary studies led to the creation of zebrafish
mutants for 96 schizophrenia-associated genes. Characterization of 59 of these mutants for altered brain
anatomy and activity has revealed 27 mutants with phenotypical abnormalities. In particular, ZNF536, a
schizophrenia-associated transcription factor, was found to be involved in the development of GABAergic
inhibitory neurons in the forebrain and cerebellum as well as regulate locomotion. During the K99 phase, this
project will complete the analysis of mutant brain anatomy. In addition, all mutants will be tested for behavioral
abnormalities, including motor behaviors associated with schizophrenia, such as defective prepulse inhibition
(Aim 1). In parallel, the developmental roles of ZNF536 will be studied to test the hypothesis that this
transcription factor is responsible for the development of GABAergic neurons, and that its loss results in the
de-inhibition of downstream circuits. To define the molecular mechanisms by which ZNF536 exerts its effects,
ZNF536 target genes will be isolated (Aim 2). Similar in-depth characterization of other interesting genes will
be undertaken in the R00 phase to discover additional pathways regulated by schizophrenia-associated genes.
Understanding the molecular, cellular, developmental and behavioral processes regulated by schizophrenia-
associated genes will provide the foundation to understand the causes of schizophrenia and develop new
diagnostics and therapies.

## Key facts

- **NIH application ID:** 10202437
- **Project number:** 5R00MH110603-05
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Summer B Thyme
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2019-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10202437

## Citation

> US National Institutes of Health, RePORTER application 10202437, Functional Analysis of Schizophrenia-Associated Genes (5R00MH110603-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10202437. Licensed CC0.

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