# Influence of DISC1 genetics on brain and behavioral development of offspring exposed to Maternal immune activation

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2023 · $16,560

## Abstract

Abstract
Epidemiological data suggest that exposure to infection during pregnancy may initiate an altered trajectory of
fetal brain development and increases risk of offspring neurodevelopmental disorders, including schizophrenia
(SZ). Animal models of maternal immune activation (MIA) have demonstrated that experimental activation of the
maternal immune system and the subsequent maternal cytokine response induces changes in offspring brain
and behavioral development in domains relevant to human neurodevelopmental disorders. While many mothers
have immune challenges during pregnancy, only a subset of the children born to those mothers develop
neurodevelopmental disorders. This hints at the potential theory that some children may be inherently
susceptible to MIA. One of the most important factors for resilience and susceptibility in MIA may be genetics,
as several disorders manifest as an interaction of genetic susceptibility and environmental risk. One gene of
particular interest is the DISC1 (Disrupted-in-schizophrenia-1) gene. DISC1 was discovered in large Scottish
pedigree and is linked to a higher incidence of SZ and SZ spectrum disorders, bipolar disorder, and mood
disorders. DISC1 has been found to be necessary for proper neurodevelopment, through associations with
embryonic and adult neurogenesis, synaptic transmission, neuronal proliferation, corticogenesis, and synapse
formation. Animal models of DISC1-/- have been used to characterize SZ pathophysiology and risk, as they mimic
the aberrant neurodevelopment that is often seen in SZ patients. The DISC1-/- model provides an opportunity to
explore gene by environment effects on MIA outcomes. Preliminary studies of DISC1-/- mice exposed to MIA
have begun to uncover promising gene by environment interactions. However, relying solely on mouse models
limits our ability to evaluate complex social and cognitive behaviors, two areas which are critical for
understanding SZ-related phenotypes. In addition, previous MIA DISC1-/- studies have not examined the
relationship of the dam’s immune response to the development of the offspring through neonatal whole brain
cytokines, behavior, and adult dopamine D2 receptor levels. We propose a novel rat model to investigate the
interactions between gene and environment in characterizing rats exposed to both LPS-induced MIA and the
DISC1 knockout. Successful completion of the proposed aims will begin uncover how genetic susceptibility may
shape MIA offspring phenotypes.

## Key facts

- **NIH application ID:** 10607339
- **Project number:** 1F31HD107818-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Simone Grant
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $16,560
- **Award type:** 1
- **Project period:** 2023-07-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10607339

## Citation

> US National Institutes of Health, RePORTER application 10607339, Influence of DISC1 genetics on brain and behavioral development of offspring exposed to Maternal immune activation (1F31HD107818-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10607339. Licensed CC0.

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