# Mouse Resource Core

> **NIH NIH P50** · NORTHWESTERN UNIVERSITY · 2024 · $209,658

## Abstract

CORE C PROJECT SUMMARY
The principal goal of this Center is to understand how gene expression and associated function within key
neuronal subtypes regulates neurobiological substrates required to form cortical circuits that enable
decision-making and behavioral adaptations. Ras and Rho-like small GTPases play fundamental biological
roles within neurons by controlling cell-autonomous growth-related signaling pathways and orchestrating
neuronal circuit assembly. Consistent with the biological importance of GTPase signaling in brain
development and function, several prominent neurodevelopmental disorder (NDD) risk genes are upstream
regulators of neuronal small GTPase signaling. We will focus on the neurobiology of two major genetic
regulators of GTPase signaling, TRIO, a top 10 risk factor for schizophrenia, and SYNGAP1, a top 10 risk
factor for ASD and intellectual disability. TRIO/SYNGAP1 are molecular effectors that orchestrate neuronal
migration, neuronal morphogenesis, synaptic connectivity, synaptic plasticity, in vivo neural circuit function,
and associated behavioral adaptations. However, it is currently unknown how their expression and function
within specific neuronal subtypes and defined developmental time windows refine cortical circuits to impact
cognitive processing and associated behaviors. Our interdisciplinary, multi-institutional “Center for GTPase
Regulation of Neuronal Cell Biology and Behavior” will study the contributions of TRIO/SYNGAP1 in cortical
circuit assembly at cellular, synapse, circuit, systems, and behavioral levels in complementary model
systems, including mouse models and human iPSC-derived neurons. The Mouse Resource Core will
facilitate studies using mouse models. Mouse somatosensory cortex shares similar overall architecture and
approximates human molecular pathways, neuronal function, and circuit organization. Thus, mouse models
are a valuable system for studying cortical development at the level of neurons, synapses, circuits and
systems, as well as for evaluating potential therapeutic strategies. The mouse genome is a tractable system
for engineering mutations in orthologous genes to enable study of genetic variants in the context of brain
tissue. Conditional deletion strategies allow for dissection of cell-type specific effects underlying synapse
and circuit dysfunction. Combining genetic manipulation with electrophysiologic and optogenetic tools,
allows for detailed, multilevel mechanistic studies in the context of an intact cortex, our Center will address
gaps in knowledge about the contribution of small GTPase regulators to cortical circuit assembly. The
primary objectives of the Mouse Resource Core are to provide centralized support of mouse model needs
for the Center Projects, including generation of novel knock-in mouse lines; maintenance and specialized
breeding of genetically modified mice; and facilitating sharing of mouse lines with the academic community.
Our centralized mouse core will provide e...

## Key facts

- **NIH application ID:** 10862391
- **Project number:** 1P50MH132775-01A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Jennifer A Kearney
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $209,658
- **Award type:** 1
- **Project period:** 2024-05-01 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862391

## Citation

> US National Institutes of Health, RePORTER application 10862391, Mouse Resource Core (1P50MH132775-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10862391. Licensed CC0.

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