Use of SCN1A knockout mice as a Dravet syndrome model and characterization of symptoms and co-morbidities

Technology Overview

Dravet syndrome is a severe, life-threatening form of epilepsy that starts in infancy and presents with an array of co-morbidities besides seizures. These include sleep disorders, ataxia, cognitive dysfunction, and in some case, a phenomenon known as sudden unexpected death in epilepsy (SUDEP). Close to 30% of epilepsy cases, including those associated with Dravet, are resistant to treatment through traditional medication regimens, making it imperative to better understand the pathways involved in these diseases to improve outcomes for epileptic patients.

Dr. Franck KalumeDr. Franck Kalume

Dr. Kalume’s team and University of Washington collaborators have developed a mouse model of Dravet syndrome that closely mirrors the primary symptoms and co-morbidities expressed in human patients. It is known that the syndrome is caused by mutations in SCN1A, a gene that produces the sodium channel NaV 1.1. Conditional knockouts of this gene in both localized and expansive regions of the mouse brain have allowed Kalume’s group to characterize how this single gene deletion can lead to a host of co-symptoms beyond seizures. Specifically, understanding the link between sleep dysfunction and prevalence of seizures has been a significant area of focus. Studies of global and conditional knock out animals showed that sleep disorders in Dravet correlate with dysfunction of GABAergic interneurons in the reticular nucleus of the thalamus (RNT), whereas seizures are linked to functional impairments of GABAergic interneurons in the hippocampus. Thus, the two symptoms may be treated by appropriate enhancement of GABAergic transmission.

A further feature of Kalume’s mouse model that makes it ideal as a model organism for Dravet syndrome is that seizures are reliably triggered following acute increases in body temperature. This allows a high control of test conditions when new medications or treatments are being investigated.

Beyond developing a more comprehensive understanding of Dravet syndrome and epilepsy as a whole, the mouse models developed by Kalume and his collaborators have the potential to serve as model organisms for studying epilepsy co-morbidities such as sleep disorders and cognitive dysfunction. Moving forward, Kalume is interested in working on collaborative projects to improve common diagnostic practices and treatments for Dravet syndrome, and potentially to develop gene-based therapies under the classification of a pediatric orphan disease treatment.

Dr. Franck Kalume’s Faces of Research Video

Stage of Development

  • Pre-clinical in vitro
  • Pre-clinical in vivo

Partnering Opportunities



  1. Williams AD, Kalume F, Westenbroek RE, Catterall WA., A more efficient conditional mouse model of Dravet syndrome: Implications for epigenetic selection and sex-dependent behaviors J Neurosci Methods. 2019 Sep 1;325:108315.
  2. Kalume F, Oakley JC, Westenbroek RE, Gile J, de la Iglesia HO, Scheuer T, Catterall WA, Sleep impairment and reduced interneuron excitability in a mouse model of Dravet SyndromeNeurobiol Dis. 2015 May;77:141-54.
  3. Cheah CS, Westenbroek RE, Roden WH, Kalume F, Oakley JC, Jansen LA, Catterall WA, Correlations in timing of sodium channel expression, epilepsy, and sudden death in Dravet syndromeChannels (Austin). 2013 Nov-Dec;7(6):468-72.
  4. Kalume F, Westenbroek RE, Cheah CS, Yu FH, Oakley JC, Scheuer T, Catterall WA, Sudden unexpected death in a mouse model of Dravet syndromeJ Clin Invest. 2013 Apr;123(4):1798-808

Learn More

To learn more about partnering with Seattle Children’s Research Institute on this or other projects, please contact:

Dr. Elizabeth Aylward, Director 
Office of Science-Industry Partnerships 
Seattle Children’s Research Institute 
818 Stewart Street, Suite 603
Seattle, WA 98101