NEXMIF/KIDLIA knockout mouse demonstrates autism-like behaviors, memory deficits, and impairments in synapse formation and function

30 31 Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental 32 disability that demonstrates impaired social interactions, communication deficits, 33 and restrictive and repetitive behaviors. ASD has a strong genetic basis and many 34 ASD-associated genes have been discovered thus far. Our previous work has 35 shown that loss of expression of the X-linked gene NEXMIF/KIDLIA is implicated 36 in patients with autistic features and intellectual disability (ID). To further 37 determine the causal role of the gene in the disorder, and to understand the 38 cellular and molecular mechanisms underlying the pathology, we have generated 39 a NEXMIF knockout (KO) mouse. We find that male NEXMIF KO mice 40 demonstrate reduced sociability and communication, elevated repetitive grooming 41 behavior, and deficits in learning and memory. Loss of NEXMIF/KIDLIA 42 expression results in a significant decrease in synapse density and synaptic 43 protein expression. Consistently, male KO animals show aberrant synaptic 44 function as measured by excitatory miniatures and post-synaptic currents in the 45 hippocampus. These findings indicate that NEXMIF KO mice recapitulate the 46 phenotypes of the human disorder. The NEXMIF KO mouse model will be a 47 valuable tool for studying the complex mechanisms involved in ASD and for the 48 development of novel therapeutics for this disorder. 49 50 51 52