The Functional Genetic Link Between Moesin Knockout And Autistic-Like Behavior

Objective: To explore whether Moesin knockout mice perform autistic-like behaviors such as impaired social novelty,and to investigate the effect of Moesin knockout on the shape and dendritic pruning function of microglia to provide new ideas for the diagnosis and treatment of autism spectrum disorders.Methods: 1)We established Moesin knockout mice through CRISPR/Cas9 technique.2)In order to investigate any behavioral abnormalities in Moesin knockout mice,we examined the mice by a series of behavioral tests such as three-chamber social test,open field test,elevated plus maze test and morris water maze test.3)We confirmed the most affected signaling pathways after knockout Moesin gene by transcriptomic analysis.4)We examined the impacts of Moesin knockout in the density,morphology,function of microglia by immunofluorescence staining and cell reconstruction by Image J software.5)We analyzed the number,shape,and classification of dendritic spines in the neuron within prefrontal cortex.6)We observed the appearance of microglia through electron microscope and analyzed their engulf function.7)Electron microscopy and immunofluorescence staining were used to evaluate the potential of microglia to perform synaptic pruning function in Moesin knockout mice.Results: 1)Moesin knockout mice model was prepared successfully.2)Moesin knockout mice performed autistic-like behavior in social novelty identify.3)The deficiency of Moesin gene resulted in the activated immune-related signaling pathways.4)Moesin was expressed in the microglia within prefrontal cortex.5)Knockout Moesin caused the significant enlargement of microglia soma as well as complexity and length of its processes in prefrontal cortex.6)Immunofluorescence staining showed the potential that microglia engulfed dendritic spines was significantly enhanced in Moesin knockout mice.7)Electron microscope observation showed that microglia were activated and its dysfunction of dendritic spines pruning.8)The dendritic spines number of neurons in prefrontal cortex was significantly reduced,especially mushroom like spines and stubby spines.9)Electron microscope observation also showed that the PSD area was significantly reduced.Conclusion: Moesin knockout mice performed autistic-like behaviors.Knockout Moesin may induce alterations of microglia within prefrontal cortex and impair its dendritic spines pruning function on synapses during the early development of neuron,which is one of the potential mechanisms that result in autism spectrum disorders.