Developing mouse models to identify novel therapeutic targets for anorexia nervosa

Abstract

Genetic influences on eating behavior and eating disorders risk emerge in adolescence; the neural substrates remain unknown. We developed a mouse model to study gene x environment interactions that promote severe self-imposed dietary restriction. Using this paradigm, we discovered a novel therapeutic target for anorexia nervosa. However, our efforts to study the underlying circuits and to translate our findings into humans were hindered by the unpredictable and low-throughout nature of the model. We have now developed an acute feeding behavioral assay that is sensitive to genetic influences (conferred by the BDNF-Val66Met gene variant) during adolescence in female mice. We are leveraging this system to apply state-of-the-art unbiased whole-brain mapping approaches to identify causal relationships between brain plasticity and abnormal feeding behaviors. This platform will accelerate our efforts to map the underlying circuits and to identify and test novel therapeutic compounds.