NEXMIF/KIDLIA Knock-out Mouse Demonstrates Autism-Like Behaviors, Memory Deficits, and Impairments in Synapse Formation and Function

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disability that demonstrates impaired social interactions, communication deficits, and restrictive and repetitive behaviors. ASD has a strong genetic basis and many ASD-associated genes have been discovered thus far. Our previous work has shown that loss of expression of the X-linked gene NEXMIF/KIDLIA is implicated in patients with autistic features and intellectual disability (ID). To further determine the causal role of the gene in the disorder, and to understand the cellular and molecular mechanisms underlying the pathology, we have generated a NEXMIF knock-out (KO) mouse. We find that male NEXMIF KO mice demonstrate reduced sociability and communication, elevated repetitive grooming behavior, and deficits in learning and memory. Loss of NEXMIF/KIDLIA expression results in a significant decrease in synapse density and synaptic protein expression. Consistently, male KO animals show aberrant synaptic function as measured by excitatory miniatures and postsynaptic currents in the hippocampus. These findings indicate that NEXMIF KO mice recapitulate the phenotypes of the human disorder. The NEXMIF KO mouse model will be a valuable tool for studying the complex mechanisms involved in ASD and for the development of novel therapeutics for this disorder.