A genetically-engineered model of Epilepsy facilitates new insights into patient behavior

Helvig, Ashley W.

Monday, 18 November 2013: 3:35 PM

Ashley W. Helvig, PhD, RN, CRNI
School of Nursing, University of West Georgia, Carrollton, GA
Michael J. Decker, PhD, RN, RRT, D.ABSM
Byrdine F. Lewis School of Nursing and Health Professions, Georgia State University, Atlanta, GA
Nikki Sawyer, BS
Department of Human Genetics, Emory University, Atlanta, GA
Andrew Escayg, PhD
Dept. of Human Genetics, Emory University, Atlanta, GA

Learning Objective 1: Explain the bench to bedside relevance of using an animal model in nursing research in which the goal is to improve human patient conditions

Learning Objective 2: Describe a specific nursing study using an animal model which recapitulates the human condition of Genetic Epilepsy with Febrile Seizures Plus.

A goal of nursing research is to build the scientific foundation for patient care (ninr.nih.gov). Animal models of human diseases are becoming increasingly employed in nursing research to address gaps in the scientific evidence and understanding of clinical conditions. These models allow researchers unique opportunities to study potentially unrecognized problems and unexplored phenomenon. Our research involves examining various aspects of epilepsy disorders associated with voltage-gated sodium channel dysfunction related to mutations within the SCN1A gene. Genetic epilepsy with febrile seizures plus (GEFS+) is one of these epilepsy disorders and is associated with a wide variety of symptom severity and age of onset (Escayg & Goldin, 2010) and may be associated with learning deficits, behavioral problems, and neuropsychiatric disorders (Mahoney et al., 2009). Most human studies of GEFS+ involve examination of the various seizure and neurological phenotypes but rarely have these studies examined behavioral phenotypes. Additionally, the impact of stress in this population is not reported. Because of the paucity of data regarding behavior and stress in persons with GEFS+, our lab examined these variables in an animal model. Animals used in the study were generated by knock-in of the human SCN1A R1648H missense mutation into the mouse Scn1a gene (Martin et al., 2010) which recapitulates the human condition of GEFS+. With this model, we have characterized increased levels of locomotor activity that are unrelated to seizure activity. We interpret this finding as preliminary evidence of sodium channel integrity as a factor contributing to symptoms of behavioral hyperactivity. Our findings suggest that animal models of epilepsy may help to provide better insight into the outcomes and mechanisms contributing to behavioral phenotypes associated with this disorder. By studying this animal model, we will now be able to concentrate efforts in our research with humans in areas we had not considered previously.

See more of: Outcomes Measurements in Chronic Conditions
See more of: Oral Paper & Poster: Science Sessions