Social behaviors and contextual memory of mutant mice are sensitive to nutrition and can be ameliorated by amino acid supplementation.

Both genetic variations and nutritional deficiency are associated with autism spectrum disorders and other neurological disorders. However, it is less clear whether or how nutritional deficiency and genetic variations influence each other under pathogenic conditions. "Valosin-containing protein" (, also known as ) is associated with multiple neurological disorders and regulates dendritic spine formation by controlling endoplasmic reticulum formation and protein synthesis efficiency. Increased protein synthesis ameliorates the dendritic spine defects of -deficient neurons. Therefore, we investigated if -deficient mice are sensitive to nutritional conditions. Here, we show that social interaction and contextual memory of -deficient mice are indeed influenced by different dietary protein levels. Moreover, leucine supplementation ameliorates the behavioral deficits and dendritic spine density of -deficient mice, strengthening evidence for the role of protein synthesis in VCP function. Our study illustrates that genetic variation and nutrient factors cross-talk to influence neuronal and behavioral phenotypes.