Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism

Abstract

Autism spectrum conditions (ASCs) are heritable conditions char-acterized by impaired reciprocal social interactions, deficits inlanguage acquisition, and repetitive and restricted behaviors andinterests. In addition to more complex genetic susceptibilities, evenmutation of a single gene can lead to ASC. Several such monogenicheritable ASC forms are caused by loss-of-function mutations ingenes encoding regulators of synapse function in neurons, includ-ingNLGN4. We report that mice with a loss-of-function mutationin the murineNLGN4orthologNlgn4, which encodes the synapticcell adhesion protein Neuroligin-4, exhibit highly selective deficitsin reciprocal social interactions and communication that are rem-iniscent of ASCs in humans. Our findings indicate that a proteinnetwork that regulates the maturation and function of synapses inthe brain is at the core of a major ASC susceptibility pathway, andestablish Neuroligin-4-deficient mice as genetic models for theexploration of the complex neurobiological disorders in ASCs.