The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Autism-like behaviours and germline transmission in transgenic monkeys overexpressing MeCP2
Abstract
Methyl-CpG binding protein 2 (MeCP2) has crucial roles in transcriptional regulation and microRNA processing. Mutations in the MECP2 gene are found in 90% of patients with Rett syndrome, a severe developmental disorder with autistic phenotypes. Duplications of MECP2-containing genomic segments cause the MECP2 duplication syndrome, which shares core symptoms with autism spectrum disorders. Although Mecp2-null mice recapitulate most developmental and behavioural defects seen in patients with Rett syndrome, it has been difficult to identify autism-like behaviours in the mouse model of MeCP2 overexpression. Here we report that lentivirus-based transgenic cynomolgus monkeys (Macaca fascicularis) expressing human MeCP2 in the brain exhibit autism-like behaviours and show germline transmission of the transgene. Expression of the MECP2 transgene was confirmed by western blotting and immunostaining of brain tissues of transgenic monkeys. Genomic integration sites of the transgenes were characterized by a deep-sequencing-based method. As compared to wild-type monkeys, MECP2 transgenic monkeys exhibited a higher frequency of repetitive circular locomotion and increased stress responses, as measured by the threat-related anxiety and defensive test. The transgenic monkeys showed less interaction with wild-type monkeys within the same group, and also a reduced interaction time when paired with other transgenic monkeys in social interaction tests. The cognitive functions of the transgenic monkeys were largely normal in the Wisconsin general test apparatus, although some showed signs of stereotypic cognitive behaviours. Notably, we succeeded in generating five F1 offspring of MECP2 transgenic monkeys by intracytoplasmic sperm injection with sperm from one F0 transgenic monkey, showing germline transmission and Mendelian segregation of several MECP2 transgenes in the F1 progeny. Moreover, F1 transgenic monkeys also showed reduced social interactions when tested in pairs, as compared to wild-type monkeys of similar age. Together, these results indicate the feasibility and reliability of using genetically engineered non-human primates to study brain disorders.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“In Rett syndrome, a severe NDD with specific cognitive and behavioral features, there is a strong PFC hypofunction with structural abnormalities [267–269].”
From Development of prefrontal cortex (2022) · cites this paper as [269]
Citations
Cites
Differential expression analysis for sequence count data
Anders, S., & Huber, W. (2010) · Genome Biology · doi:10.1186/gb-2010-11-10-r106 · Cited by 15,581
Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2
Amir, R. E., Van den Veyver, I. B., Wan, M., Tran, C. Q., Francke, U., & Zoghbi, H. Y. (1999) · Nature Genetics · doi:10.1038/13810 · Cited by 4,990
MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription
Chahrour, M., Jung, S. Y., Shaw, C., Zhou, X., Wong, S. T. C., Qin, J., & Zoghbi, H. Y. (2008) · Science · doi:10.1126/science.1153252 · Cited by 1,823
MeCP2 Is a Transcriptional Repressor with Abundant Binding Sites in Genomic Chromatin
Nan, X., Campoy, F. J., & Bird, A. P. (1997) · Cell · doi:10.1016/s0092-8674(00)81887-5 · Cited by 1,288
MapSplice: Accurate mapping of RNA-seq reads for splice junction discovery
Wang, K., Singh, D., Zeng, Z., Coleman, S. J., Huang, Y., Savich, G. L., He, X., Mieczkowski, P., Grimm, S. A., Perou, C. M., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq622 · Cited by 1,193
Generation of transgenic non-human primates with germline transmission
Sasaki, E., Suemizu, H., Shimada, A., Hanazawa, K., Oiwa, R., Kamioka, M., Tomioka, I., Sotomaru, Y., Hirakawa, R., Eto, T., et al. (2009) · Nature · doi:10.1038/nature08090 · Cited by 712
Identification of a mammalian protein that binds specifically to DNA containing methylated CpGs
Meehan, R. R., Lewis, J., McKay, S. J., Kleiner, E., & Bird, A. P. (1989) · Cell · doi:10.1016/0092-8674(89)90430-3 · Cited by 677
Mild overexpression of MeCP2 causes a progressive neurological disorder in mice
Collins, A. L., Levenson, J. M., Vilaythong, A. P., Richman, R., Armstrong, D. L., Noebels, J. L., David Sweatt, J., & Zoghbi, H. Y. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh282 · Cited by 626
Young, J. I., Hong, E. P., Castle, J. C., Crespo-Barreto, J., Bowman, A. B., Rose, M. F., Kang, D., Richman, R., Johnson, J. M., Berget, S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507856102 · Cited by 484
Early determinants of behaviour: evidence from primate studies
Suomi, S. J. (1997) · British Medical Bulletin · doi:10.1093/oxfordjournals.bmb.a011598 · Cited by 483
Flagged first, then by citations
Cited by
Sorted by citations
Items 301–322 of 322
Ströckens, F., & Amunts, K. (2024) · Oxford University Press eBooks · doi:10.1093/med/9780197676592.003.0002
Lee, D.-H., Yoon, S., Jo, Y., Mo, J. W., Kwon, J., Lee, S. I., Kwon, J., & Kim, J.-S. (2024) · Frontiers in Veterinary Science · doi:10.3389/fvets.2024.1452631
CRISPR/Cas9-based genetic engineering for translational research in neurological disorders
Megagiannis, P., Rouleau, G. A., & Zhou, Y. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-19041-4.00021-2
Poo, M.-M. (2024) · Cell · doi:10.1016/j.cell.2024.09.017
Ren, X., Wang, H., Lv, X., Zhou, Y., Fan, Y., Yu, Y., Turck, C. W., Chen, Y., Lv, L., Hu, Y., et al. (2024) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.b2400294
Methods for In Vivo Gene Manipulation
Monteggia, L. M., & Xu, W. (2025) · Oxford University Press eBooks · doi:10.1093/med/9780197640654.003.0004
Neocortex Folding in Primates up to Human: Evolution and Mechanisms
Long, K. R., Huttner, W. Β., & Namba, T. (2025) · Developmental Neuroscience · doi:10.1159/000547228
Genetically Modified Primate Models for Brain Disorder Research
Yang, Y., Lin, J., Li, M., Yang, L., Lu, Z., & Yan, T. (2025) · Neuroscience Bulletin · doi:10.1007/s12264-025-01529-7
Stereotaxic Injection of Lentiviral Vectors into the Primate Brain
Inoue, K., & Takada, M. (2025) · Methods in molecular biology · doi:10.1007/978-1-0716-4807-0_4
Contributions of nonhuman primate research to unraveling the social brain and its impairments
Gacoin, M., Jiang, H., Obliger-Debouche, M., Cléry, J. C., & Sliwa, J. (2025) · Revue de primatologie · doi:10.4000/15cqb · Cited by 1
Qiu, S., Qiu, Y., Li, Y., Zhu, X., Liu, Y., Qiao, Y., Cheng, Y., & Liu, Y. (2023) · Figshare · doi:10.6084/m9.figshare.22616888
The emerging role of gene therapy in autism spectrum disorder
Shokoohi, M., Ghamin, K., Ghaderi, M., Bamarinejad, F., Baker, A. H., Danafar, N., & Zafarshamspour, S. (2026) · Discover Mental Health · doi:10.1007/s44192-026-00425-4
Uncovering the sleep pathway in the social profile of Rett syndrome
Zhang, X. (2022) · theses.fr (ABES) · doi:10.70675/5bb1442czcae0z4a69zb3a7zf6e99af7583e
Self-citationBo, T., Huang, Y., Lu, Y., Song, Y., Zhang, J., Zhang, J., Wang, H., & Wang, Z. (2026) · Neuroscience Bulletin · doi:10.1007/s12264-026-01627-0
Self-citationShen, P.-X., Wang, P., & Wang, H. (2026) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-026-01740-8
Marmoset Models for the Study of Autism Spectrum Disorder
Menegas, W., Zhang, Q., & Feng, G. (2026) · Biological Psychiatry · doi:10.1016/j.biopsych.2026.05.013
Non-human primates as a model for human development.
築山, 智., NAKAMURA, T., FUJIWARA, K., Saitou, M., & Tsukiyama, T. (n.d.) · Institutional Repositories DataBase (IRDB)
Prdm15 Deficiency Results in Impaired Hippocampal Neurogenesis and Autism-Like Behaviors
Dong, Q., Xiao, W., Sun, Z., Sun, Z., & Wang, Y. (2026) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-026-01770-2
Self-citationMECP2 -mutant marmosets exhibit primate-specific phenotypes of Rett syndromePreprint
Kishi, N., Okahara, J., Sato, K., Yoshimaru, D., Kurotaki, Y., Onishi, K., Sanosaka, T., Henry, R., Ito, T., Okuno, M., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.26.734672 · Cited by 1
Emerging gene-edited dog models for autism spectrum disorder
Yuan, S., Shi, Q., Zhao, H., Guo, K., Jiang, Y., & Zhang, Y. (2026) · Genomic psychiatry : · doi:10.61373/gp026p.0036
Self-citationLan, Z.-G., Onoe, H., Tsukiyama, T., Iwatani, C., Chen, C.-Y., Okita, K., Ishizuka, K., Endo, R., Nakai, R., Imamura, K., et al. (2026) · bioRxiv · doi:10.64898/2026.10.11.758339
Metadata
- Authors
- Liu, Z., Li, X., Zhang, J.-T., Cai, Y.-J., Cheng, T.-L., Cheng, C., Wang, Y., Zhang, C.-C., Nie, Y.-H., Chen, Z.-F., Bian, W.-J., Zhang, L., Xiao, J., Lu, B., Zhang, Y.-F., Zhang, X.-D., Sang, X., Wu, J.-J., Xu, X., Xiong, Z.-Q., Zhang, F., Yu, X., Gong, N., Zhou, W.-H., Sun, Q., & Qiu, Z.
- Affiliations
- Chinese Academy of Sciences (CN)
- Fudan University (CN)
- Corresponding author
- Sun, Qiang
- Qiu, Zilong
- ORCID
- Venue
- Nature
- Published
- 2016-01-25
- Volume
- 530
- Issue
- 7588
- Pages
- 98-102
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2261151942
- Cited by
- 322
- References
- 45
- Citations by year
- 2026: 12 · 2025: 26 · 2024: 26 · 2023: 22 · 2022: 32 · 2021: 44 · 2020: 30 · 2019: 32 · 2018: 27 · 2017: 39 · 2016: 30
- FWCI
- 34.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- MECP2 duplication syndrome, Rett syndrome, autism-like behavior, social interaction deficits, anxiety, germline transmission, stress response, neurodevelopmental disorders, nonhuman primate model, stereotypy, cognitive function
- MeSH terms
- Animals, Anxiety, Autistic Disorder, Brain, Cognition, Disease Models, Animal, Female, Humans, Locomotion, Macaca fascicularis, Male, Phenotype, Social Behavior, Germ-Line Mutation, Transgenes, Sperm Injections, Intracytoplasmic, Animals, Genetically Modified, Heredity, Methyl-CpG-Binding Protein 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
