The Effect Of Overexpressing Microtubule-associated STOP Protein On Behaviors Of BTBR Mice

Objective:The aim of the study is to investigate the effects of enhanced STOP gene expression on the autism-like behaviors of the BTBR mice by enhancing the expression of STOP protein in the brain of the BTBR mice which is the autistic animal models and testing the social behavioral ability and repeated behavior of the BTBR mice in experimental group and control group.Methods:1.Using multisite Gateway clone technique to construct expression vector of p LV[Exp]-m Cherry:T2A:Puro-EF1A>STOP.The STOP overexpressed lentivirus were injected into the lateral ventricle of P0 BTBR mice to enhance the expression of STOP protein in the brain of experimental BTBR mice,and the control group was given blank control lentivirus without exogenous gene.2.The cerebral cortex of BTBR mice in the experimental group and BTBR mice in the control group were sampled,and western blotting was performed to understand the expression of STOP protein in the cerebral cortex of each group,3.In order to understand the effect of overexpression of microtubule-associated protein STOP on autistic BTBR mice,the 8-weeks-old BTBR mice in the experimental group and the control group were tested with repetitive behavior test using self-grooming behavior test and social behavior ability test using 3-compartment communication test system.4.Statistical methods: t-test was used to compare the differences between self-grooming behavior’s and western blotting’s results of the experimental group and the control group.In 3-compartment communication tests,we used two-way ANOVA analysis and Bonferroni’s multiple comparison.Results:1.Compared with the mice of control group,the expression level of STOP protein in the cerebral cortex of experimental BTBR mice was increased,but there was no statistical difference(t=1.632,P=0.1781).2.Compared with the control group,the self-grooming time of BTBR mice in the experimental group tended to decrease,but there was no statistical difference(P= 0.069).3.Compared with the control group,the experimental group BTBR mice showed significant social preference(P<0.01).Conclusion:This study suggests that enhancing the expression of microtubule-associated STOP/MAP6 protein in the brain of BTBR mice can improve social preference of the BTBR mice.This study validated the important role of microtubule-binding protein STOP in autism spectrum disorder.