# Validation of a novel mouse model of temporal lobe epilepsy

> **NIH NIH R61** · UNIVERSITY OF VIRGINIA · 2020 · $363,375

## Abstract

Project summary
 The long-term goal of these studies is to develop novel therapeutics for epilepsy patients whose seizures are
not well-controlled by current drugs (pharmacoresistant). Many of these patients have a type of focal epilepsy
called temporal lobe epilepsy (TLE). There has been little progress in the development of novel therapies for
these patients because of the lack of suitable animal models. Current TLE models show much greater neuronal
death and hippocampal sclerosis than observed in patients, and a highly variable occurrence of seizures that
precludes drug testing. The proposed studies will validate the usefulness of new mouse model of TLE that
overcomes these problems. It was discovered that a mild kindling protocol of a specific strain of mice, VGAT-
Cre, led to spontaneous seizures. Kindling refers to the process where repeated electrical stimulations eventually
trigger tonic-clonic seizures. However, kindling only leads to spontaneous seizures in VGAT-Cre mice. These
mice express Cre recombinase under the control of the vesicular GABA transporter (VGAT), a gene that is
specifically expressed in GABAergic inhibitory neurons. Loss, or dysfunction, of these neurons in the
hippocampus has been linked to the development of temporal lobe epilepsy. The first aim of this study will
optimize kindling protocols to generate mice with an ideal frequency of spontaneous seizures for drug testing.
The second aim is to validate that these mice respond to currently available antiseizure drugs. This work will be
done by Dr. Wilcox’s group at the University of Utah, who also directs the NIH-sponsored Epilepsy Therapy
Screening Program.

## Key facts

- **NIH application ID:** 9984553
- **Project number:** 5R61NS112549-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Edward Perez-Reyes
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $363,375
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984553

## Citation

> US National Institutes of Health, RePORTER application 9984553, Validation of a novel mouse model of temporal lobe epilepsy (5R61NS112549-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984553. Licensed CC0.

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