# Transgenic Drosophila melanogaster Carrying a Human Full-Length DISC1 Construct (UAS-hflDISC1) Showing Effects on Social Interaction Networks

## TL;DR

This study shows that inserting a human DISC1 gene into fruit flies affects their social behavior and motor functions, similar to symptoms seen in human mental illnesses.

## Contribution

The study introduces a new transgenic Drosophila model with human DISC1 to explore its impact on social and motor behaviors.

## Key findings

- Transgenic flies showed altered social interaction networks and locomotor activity.
- Increased hydrogen peroxide and decreased glutathione levels suggest redox regulation changes.
- Phenotypes indicate altered motor functions and nervous system functioning.

## Abstract

Disrupted in Schizophrenia 1 (DISC1) is a scaffold protein implicated in major mental illnesses including schizophrenia, with a significant negative impact on social life. To investigate if DISC1 affects social interactions in Drosophila melanogaster, we created transgenic flies with second or third chromosome insertions of the human full-length DISC1 (hflDISC1) gene fused to a UAS promotor (UAS-hflDISC1). Initial characterization of the insertion lines showed unexpected endogenous expression of the DISC1 protein that led to various behavioral and neurochemical phenotypes. Social interaction network (SIN) analysis showed altered social dynamics and organizational structures. This was in agreement with the altered levels of the locomotor activity of individual flies monitored for 24 h. Together with a decreased ability to climb vertical surfaces, the observed phenotypes indicate altered motor functions that could be due to a change in the function of the motor neurons and/or central brain. The changes in social behavior and motor function suggest that the inserted hflDISC1 gene influences nervous system functioning that parallels symptoms of DISC1-related mental diseases in humans. Furthermore, neurochemical analyses of transgenic lines revealed increased levels of hydrogen peroxide and decreased levels of glutathione, indicating an impact of DISC1 on the dynamics of redox regulation, similar to that reported in transgenic mammals. Future studies are needed to address the localization of DISC1 expression and to address how the redox parameter changes correlate with the observed behavioral changes.