Cell Reports. 2021 Nov 2
Kan Yang, Yuhan Shi, Xiujuan Du, Jincheng Wang, Yuefang Zhang, Shifang Shan, Yiting Yuan, Ruoqing Wang, Chenhuan Zhou, Yuting Liu, Zilin Cai, Yanzhi Wang, Liu Fan, Huatai Xu, Juehua Yu, Jinke Cheng, Fei Li, Zilong Qiu
Products used in the paper Details Operation
AAV9-hSyn-SENP1-C603S-EGFP; AAV9-hSyn-FMRP-K88R-K130R-EGFP AAV9-hSyn-EGFP (Serotype 9, titer 8.5x 10^14 vg/ mL), AAV9-hSyn-SENP1-EGFP (Serotype 9, titer 4.1x 10^13 vg/mL), AAV9-hSyn-SENP1-C603S-EGFP (Serotype 9, titer 4.1×10^13 vg/mL), AAV9-hSyn-FMRP-EGFP (Serotype 9, titer 4×10^13 vg/mL) and AAV9-hSyn-FMRP-K88RK130R-EGFP (Serotype 9, titer 6.2×10^13 vg/mL) were purchased from Institute of Neuroscience Gene Editing Core and PackGene Bioscience, Co, Guangzhou. Request Quote

Research Field: CNS

AAV Serotype: AAV9

Dose: Virus stocks were diluted to 1×10^12 vg/ml, and 0.2 mL virus was injected with a speed of 30 nl/min by a micro-injector and micro-infusion pump (PHD 2000, Harvard Apparatus). For the sparse labeling experiment, the AAV9-hSyn-Cre was diluted to 1×10^8 vg/ml, and the AAV9-CAG-FLEX-EGFP was diluted to 1×10^13 vg/ml. About 0.2 mL mixed virus was injected into RSA with a speed of 30 nl/min. After injection, the mice were kept on a warm blanket to maintain the body temperature until fully awake.

Routes of Administration: viruses were injected into the retrosplenial agranular cortex (RSA) bilaterally according to standard mouse brain atlas

Targeted organ: brain

Animal or cell line strain: C57BL/6N mice


Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder, causing defects of social interaction and repetitive behaviors. Here, we identify a de novo heterozygous gene-truncating mutation of the Sentrin-specific peptidase1 (SENP1) gene in people with ASD without neurodevelopmental delay. We find that Senp1+/− mice exhibit core autistic-like symptoms such as social deficits and repetitive behaviors but normal learning and memory ability. Moreover, we find that inhibitory and excitatory synaptic functions are severely affected in the retrosplenial agranular (RSA) cortex of Senp1+/− mice. Lack of Senp1 leads to increased SUMOylation and degradation of fragile X mental retardation protein (FMRP), also implicated in syndromic ASD. Importantly, re-introducing SENP1 or FMRP specifically in RSA fully rescues the defects of synaptic function and autistic-like symptoms of Senp1+/− mice. Together, these results demonstrate that disruption of the SENP1-FMRP regulatory axis in the RSA causes autistic symptoms, providing a candidate region for ASD pathophysiology.

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