Evidence map›Paper›PMID 30329048›Full record

ArticleHuman molecular genetics2019

CRISPR/Cas9-mediated disruption of SHANK3 in monkey leads to drug-treatable autism-like symptoms.

Zhuchi Tu, Hui Zhao, Bang Li, Sen Yan, Lu Wang, Yongjin Tang, Zhujun Li, Dazhang Bai, Caijuan Li, Yingqi Lin and 7 more

Abstract read
In one paragraph

Article in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
2.8field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 71 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 2 countries.

Zhuchi TuGuangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, China.
Hui ZhaoState Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Bang LiGuangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, China.
Sen YanGuangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, China.
Lu WangDepartment of Nuclear Medicine and PET/CT-MRI Center, the First Affiliated Hospital of Jinan University & Institute of Molecular and Functional Imaging, Jinan University, Guangzhou China.
Yongjin TangDepartment of Nuclear Medicine and PET/CT-MRI Center, the First Affiliated Hospital of Jinan University & Institute of Molecular and Functional Imaging, Jinan University, Guangzhou China.
Zhujun LiGuangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, China.
Dazhang BaiGuangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, China.
Caijuan LiGuangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, China.
Yingqi LinGuangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, China.
Yuefeng LiGuangdong Landau Biotechnology Co. Ltd., Guangzhou, China.
Jianrong LiuYuanxi Biotech Inc., Guangzhou China.
Hao XuDepartment of Nuclear Medicine and PET/CT-MRI Center, the First Affiliated Hospital of Jinan University & Institute of Molecular and Functional Imaging, Jinan University, Guangzhou China.
Xiangyu GuoGuangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, China.
Yong-Hui JiangDepartment of Pediatrics and Department of Neurobiology, Duke University, Durham, NC, USA.
Yong Q ZhangState Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Xiao-Jiang LiGuangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, China.
Jinan University · CNFirst Affiliated Hospital of Jinan University · CNChinese Academy of Sciences · CNDuke University · US

Funding

Neuronal function of huntingtin-associated proteinR01NS036232 · NINDS · EMORY UNIVERSITY · PI ESCAYG, ANDREW P · 1998 to 2021
$6.7M
N-terminal huntingtin and Huntington disease neuropathologyR01NS101701 · NINDS · EMORY UNIVERSITY · PI ESCAYG, ANDREW P · 2017 to 2021
$2.2M
NINDS NIH HHS R01 NS036232NINDS NIH HHS R01 NS101701
6 · The paper itself

Abstract

Monogenic mutations in the SHANK3 gene, which encodes a postsynaptic scaffold protein, play a causative role in autism spectrum disorder (ASD). Although a number of mouse models with Shank3 mutations have been valuable for investigating the pathogenesis of ASD, species-dependent differences in behaviors and brain structures post considerable challenges to use small animals to model ASD and to translate experimental therapeutics to the clinic. We have used clustered regularly interspersed short palindromic repeat/CRISPR-associated nuclease 9 to generate a cynomolgus monkey model by disrupting SHANK3 at exons 6 and 12. Analysis of the live mutant monkey revealed the core behavioral abnormalities of ASD, including impaired social interaction and repetitive behaviors, and reduced brain network activities detected by positron-emission computed tomography (PET). Importantly, these abnormal behaviors and brain activities were alleviated by the antidepressant fluoxetine treatment. Our findings provide the first demonstration that the genetically modified non-human primate can be used for translational research of therapeutics for ASD.

Indexed as

AnimalsAutism Spectrum DisorderBehavior, AnimalBrainCRISPR-Cas SystemsDisease Models, AnimalExonsFluoxetineHumansInterpersonal RelationsMacaca fascicularisMiceMutationNerve Tissue ProteinsFluoxetineNerve Tissue ProteinsSHANK3 protein, human

Identifiers

PMID30329048
PMCPMC6489410
OpenAlexW2896590045

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.