# A novel mouse model for anxiety-induced seizures

> **NIH NIH R03** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2020 · $77,000

## Abstract

Project Summary
Although epilepsy is diagnosed as unprovoked seizures, it is generally accepted that seizures can be precipitated
in epileptic individuals by endogenous and exogenous stimulants. Stress and anxiety are among the most
frequently reported precipitants for seizures in epileptic individuals. Understanding the pathophysiology of
anxiety-induced seizures can dramatically benefit management of epileptic patients. Here, we present
preliminary data for a novel mouse model for anxiety-induced seizures. The model is regulated by cre-induced
expression of a human BK-type potassium channel gene containing an epilepsy mutation (D369G transgene).
Preliminary studies indicate the D369G mice have increased anxiety, and handling-induced epileptic seizures.
Our overarching hypothesis is that these transgenic mice will serve as a model for anxiety-induced seizures in
epilepsy. As a first step to understanding anxiety-induced seizures, we propose an R03 pilot study to identify the
regions of the brain where expression of the D369G causes seizures. We propose two aims. For aim 1, we will
more thoroughly characterize the mouse phenotypes and screen the remaining founder lines for handling-
induced seizures. By also crossing D369G lines to the BK channel knockout mice, we will eliminate endogenous
expression and determine if D369G transgene expression reflects the normal BK channel expression pattern.
For aim 2, we will use tissue and developmental-specific cre driver lines to determine the brain region/s
responsible for the D369G phenotype. We hypothesize that handling-induced seizures are mediated by D369G
BK channel post-development expression in excitatory cells of the hippocampus. Using temporal and tissue-
specific cre driver lines we will examine 1) if prenatal or postnatal expression is required for the phenotype, 2) if
excitatory or inhibitory neurons confer the phenotype, or 3) if expression in the hippocampus or amygdala confer
increased anxiety and handling induced seizures. Success of this proposal will create a foothold for future in-
depth electrophysiology studies regarding how activity in the identified brain region intersects with anxiety to
precipitate seizures, and potentially provide drug targets to prevent or limit stress-induced seizure onset.

## Key facts

- **NIH application ID:** 10244725
- **Project number:** 3R03NS114906-01A1S1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** ROBERT BRENNER
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $77,000
- **Award type:** 3
- **Project period:** 2020-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10244725

## Citation

> US National Institutes of Health, RePORTER application 10244725, A novel mouse model for anxiety-induced seizures (3R03NS114906-01A1S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10244725. Licensed CC0.

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