Autism-like behaviours and germline transmission in transgenic monkeys overexpressing MeCP2

Liu, Zhen; Li, Xiao; Zhang, Juntao; Cai, Yijun; Cheng, Tian-Lin; Cheng, Cheng; Wang, Yan; Zhang, Chenchen; Nie, Yanhong; Chen, Zhifang; Bian, Wenjie; Zhang, Ling; Xiao, Jianqiu; Lu, Bin; Zhang, Yuefang; Zhang, Xiaodi; Sang, Xiao; Wu, Jia-Jia; Xu, Xiu; Xiong, Zhi‐Qi; Zhang, Feng; Yu, Xiang; Gong, Ningqiang; Zhou, Wenhao; Sun, Qiang; Qiu, Zilong

doi:10.1038/nature16533

Cited by 261 publications

(206 citation statements)

References 42 publications

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“…It clearly demonstrates the importance of this epigenetically-selective 5mC binding protein in the maturation of the central nervous system [38]. Furthermore, evidence in mice indicates it is required even in adulthood for correct neurological function [39] and additionally overexpression of MECP2 leads cynomolgus monkeys to display autistic behaviours [40]. Data has accrued that the MECP2 protein may also bind 5hmC in neuronal cells [41], as well as non-CpG methylated cytosines as the neuron matures [42,43], indicating the potential epigenetic complexity in brain disorders [44].…”

Section: Dna Modificationsmentioning

confidence: 87%

Insights in human epigenomic dynamics through comparative primate analysis

Bell

2016

Genomics

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Epigenomic analysis gives a molecular insight into cell-specific genomic activity. It provides a detailed functional plan to dissect an organism, tissue by tissue.Therefore comparative epigenomics may increase understanding of human-acquired traits, by revealing regulatory changes in systems such as the neurological, musculoskeletal, and immunological.Enhancer loci evolve fast by hijacking elements from other tissues or rewiring and amplifying existing units for human-specific function. Promoters by contrast often require a CpG dense genetic infrastructure. Specific interplay occurs between the two, but also a shared modality of function, with coordination from global chromatin-modifying enzymes. Changes in specific transcription factor binding sites also facilitate the local epigenetic state. In the case of CTCF, these may further influence 3-dimensional structure and interaction.How these mechanistic units are modulated between tissue and species enables more comprehensive understanding of human processes and pathology.With this, precise therapeutic targeting of these epigenetic modifications may become possible.

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Section: Dna Modificationsmentioning

confidence: 87%

Insights in human epigenomic dynamics through comparative primate analysis

Bell

2016

Genomics

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“…The work is moving most quickly in China and Japan. In January, for instance, neuroscientist Zilong Qiu and his colleagues at the Chinese Academy of Sciences in Shanghai published a paper 15 describing macaques with a CRISPR-induced mutation in MECP2, the gene associated with the neurodevelopmental disorder Rett syndrome. The animals showed symptoms of autism spectrum disorder, including repetitive behaviours and avoiding social contact.…”

Section: I S E a S E M O D E L Smentioning

confidence: 99%

Welcome to the CRISPR zoo

Reardon¹

2016

Nature

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“…As a result, two F1 animals harboring the transgene derived from the founder animal were obtained. Macaque offspring with the autismassociated methyl-CpG-binding protein 2 (MeCP2) transgene have been successfully acquired by intracytoplasmic injection of sperm, which was developed in xenografted testicular tissue in immunodeficient mice [9,10]. Phenotypic analysis of these offspring showed that social interactions were reduced in F1 animals compared to the wild type.…”

Section: Development Of Genetically Engineered Nhpsmentioning

confidence: 99%

Genetic engineering in nonhuman primates for human disease modeling

Sato

Sasaki

2017

J Hum Genet

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Nonhuman primate (NHP) experimental models have contributed greatly to human health research by assessing the safety and efficacy of newly developed drugs, due to their physiological and anatomical similarities to humans. To generate NHP disease models, drug-inducible methods, and surgical treatment methods have been employed. Recent developments in genetic and developmental engineering in NHPs offer new options for producing genetically modified disease models. Moreover, in recent years, genome-editing technology has emerged to further promote this trend and the generation of disease model NHPs has entered a new era. In this review, we summarize the generation of conventional disease model NHPs and discuss new solutions to the problem of mosaicism in genome-editing technology.

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Autism-like behaviours and germline transmission in transgenic monkeys overexpressing MeCP2

Cited by 261 publications

References 42 publications

Insights in human epigenomic dynamics through comparative primate analysis

Insights in human epigenomic dynamics through comparative primate analysis

Welcome to the CRISPR zoo

Genetic engineering in nonhuman primates for human disease modeling

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