〔Abstract〕 Abstract Objective To establish a novel autistic juvenile rat model with down-regulation of PTEN gene (PTEN- ASD) , to compare the newly constructed animal model with two traditional autistic animal models of Valproic acid (VPA) and adenovirus (ADV) , and ultimately to prove the advantages of this model in animal model establishment of acupuncture treatment for ASD. Methods Wista rats at 12. 5 days of gestation were randomly divided into 2 groups . VPA rats were given 600 mg/kg of normal saline (NS) intraperitoneally. Weight , eye opening time and tail deformity were recorded . The newborn mice in NS group were randomly divided into three groups ( 10 rats in each group) : normal (NS) group , virus (ADV) group and virus-negative control (ADV-NC) group; VPA group (20 young rats) was randomly divided into 2 groups (10 rats in each group) : valproic acid (VPA) group and val- proic acid-binding virus interference (VPA + ADV) group . The body weight , tail length , curved tail , geotaxis text time and skeletal deformity of 5 groups of young rats after birth , the neurobehavioral behavior of 21-day-old rats , and the myelin structure of brain tissue under electron microscope were observed , the expression levels of PTEN , PI3K , AKT , GSK3 βand MBP were detected by immunohistochemistry , Western blot and q-PCR. Results Com- pared with the NS group , the VPA group had significantly increased malformation rate , slow weight gain , slow tail length growth , and long negative geotaxis reflex time (P < 0. 05) . Compared with the NS group , the weight gain , tail length growth and negative geotaxis reflex time of the three model groups were slower (P < 0. 05) , and the per- formance of model 3 was the most significant. There were significant differences in the time of crossing the central grid , the number of crossing the edge grid , and the time of crossing the edge grid in the open field test between the three groups and the NS group (P < 0. 05) . In the self-grooming experiment , the number of interactions in Model 3 was the least (P < 0. 05) , and the number of digging and self-grooming was the most (P < 0. 05) . The three-box social experiment model 3 had the shortest average number of entries into the social box and the shortest residence time (P < 0. 05) . The longer it took to find the platform in the water maze experiment , the fewer times it crossed the third quadrant (P < 0. 05) . The structure of the myelin sheath layer in the corpus callosum was observed by transmission electron microscopy. The structure of the NS group was clear and complete . Compared with the NS group , the myelin structure of the ADV-NC group was similar , and the myelin structure of the three model groups was stratified and broken , and there were pathological changes and myelin damage in the ASD . Among them , the myelin sheath of the model 3 was thickened , stratified , and severe visible disintegration . The results of immunohis- tochemistry , Western blot and q-PCR showed that the expression of PTEN in model 3 was down-regulated by about 50% , which was the most obvious . The expression of AKT and MBP increased , and the expression of GSK3 βde- creased (P < 0. 05) . However , the results of q-PCR showed that the expression of PI3K-mRNA in the three model groups significantly increased (P < 0. 05) , and the change of model 3 was the most significant. Conclusion The novel PTEN-ASD animal model established by VPA + ADV method is observed to have significant pathological changes that are typical of the manifestation of ASD myelin dysplasia and is determined to have better results than the two traditional autistic animal models .