Spescial Issues

Autistic-like behaviors by MECP2 transgenic monkeys and germline transmission

  • QIU Zilong ,
  • LI Xiao
  • State Key Laboratory of Neuroscience, Institute of Neuroscience, Chinese Academy of Sciences, CAS Center for Excellence in Brain Science and Intelligence Technology(CEBSIT), Shanghai 200031, China

Received date: 2017-11-30

  Revised date: 2018-03-08

  Online published: 2018-04-27


Autism is a neurological disease with high public concern in recent years. Methyl-CpG binding protein 2(MeCP2) plays an important role in autism for its importance in transcriptional regulation and microRNA processing. Mutations in MeCP2 gene are found in most of patients with Rett syndrome, duplications of MeCP2-containing genomic segments cause the MeCP2 duplication syndrome, which shares core symptoms with autism spectrum disorders. Although MeCP2 transgenic mice has already been reconstructed, it is still difficult to identify autism-like behaviours in the mouse model of MeCP2 overexpression. In this article we report the lentivirus-based transgenic cynomolgus monkeys expressing human MeCP2 in the brain. Genomic integration sites of the transgenes are characterized by a deepsequencing-based method and expression of the MeCP2 transgene is confirmed by Western blotting. This type of transgenic monkeys exhibits autism-like behaviours in action, social and emotional aspects and shows germline transmission of the transgene. These results indicate the feasibility and reliability of using genetically engineered non-human primates to study brain disorders.

Cite this article

QIU Zilong , LI Xiao . Autistic-like behaviors by MECP2 transgenic monkeys and germline transmission[J]. Science & Technology Review, 2018 , 36(7) : 48 -55 . DOI: 10.3981/j.issn.1000-7857.2018.07.008


[1] Eisenberg L. Child psychiatry. Mental deficiency[J]. American Journal of Psychiatry, 1949, 120(114):526-528.
[2] Caronna E B, Milunsky J M, Tagerflusberg H. Autism spectrum disorders:Clinical and research frontiers[J]. Archives of Disease in Childhood, 2008, 93(6):518-523.
[3] Rapin I, Tuchman R F. Autism:Definition, neurobiology, screening, diagnosis[J]. Pediatric Clinics of North America, 2008, 55(5):1129-1146.
[4] Noens I, Van B I, Verpoorten R, et al. The ComFor:An instrument for the indication of augmentative communication in people with autism and intellectual disability[J]. Journal of Intellectual Disability Research, 2006, 50(9):621-632.
[5] Lam K S L, Aman M G. The repetitive behavior scale-revised:Independent validation in individuals with autism spectrum disorders[J]. Journal of Autism & Developmental Disorders, 2007, 37(5):855-866.
[6] Delorme R, Ey E, Toro R, et al. Progress toward treatments for synaptic defects in autism[J]. Nature Medicine, 2013, 19(6):685-694.
[7] Azevedo F, Carvalho L L, Farfel J, et al. Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain[J]. Journal of Comparative Neurology, 2009, 513(5):532-541.
[8] Herculano-Houzel S. The remarkable, yet not extraordinary, human brain as a scaled-up primate brain and its associated cost[J]. PNAS, 2012, 109(Suppl 1):10661-10668.
[9] Suzana H H. The human brain in numbers:A linearly scaledup primate brain[J]. Frontiers in Human Neuroscience, 2009, 3(31):31.
[10] Gray E G. Axo-somatic and axo-dendritic synapses of the cerebral cortex:An electron microscope study[J]. Journal of Anatomy, 1959, 93(4):420-433.
[11] Chang H T. Cortical neurons with particular reference to the apical dendrites[J]. Cold Spring Harbor Symposia on Quantitative Biology, 1952, 17(7):189-202.
[12] Yuste R. Electrical compartmentalization in dendritic spines[J]. Annual Review of Neuroscienc, 2013, 36(1):429-449.
[13] Sheng M, Kim E. The Postsynaptic organization of synapses[J]. Cold Spring Harbor Perspectives in Biology, 2011, 3(12):VⅡ.
[14] Delorme R, Ey E, Toro R, et al. Progress toward treatments for synaptic defects in autism[J]. Nature Medicine, 2013, 19(6):685-694.
[15] Meehan R R, Lewis J D, Mckay S, et al. Identification of a mammalian protein that binds specifically to DNA containing methylated CpGs[J]. Cell, 1989, 58(3):499-507.
[16] Nan X, Campoy F J, Bird A A. MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin[J]. Cell, 1997, 88(4):471-481.
[17] Young J I, Hong E P, Castle J C, et al. Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2[J]. PNAS, 2005, 102(49):17551-17558.
[18] Cheng T L, Wang Z, Liao Q, et al. MeCP2 suppresses nuclear microrna processing and dendritic growth by regulating the DGCR8/Drosha complex[J]. Developmental Cell, 2014, 28(5):547-560.
[19] Amir R E, Ib V D V, Wan M, et al. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpGbinding protein 2[J]. Nature Genetics, 1999, 23(2):185-188.
[20] Ramocki M B, Peters S U, Tavyev Y J, et al. Autism and other neuropsychiatric symptoms are prevalent in individuals with MECP2 duplication syndrome[J]. Annals of Neurology, 2009, 66(6):771-782.
[21] Samaco R C, Mandel-Brehm C, McGraw C M, et al. Crh and Oprm1 mediate anxiety-related behavior and social approach in a mouse model of MECP2 duplication syndrome[J]. Nature Genetics, 2012, 44:206-211.
[22] Collins A L, Levenson J M, Vilaythong A P, et al. Mild overexpression of MeCP2 causes a progressive neurological disorder in mice[J]. Human Molecular Genetics, 2004, 13(21):2679-89.
[23] Nakagawa T, Feliu-Mojer M I, Wulf P, et al. Generation of lentiviral transgenic rats expressing Glutamate Receptor Interacting Protein I (GRIP1) in brain, spinal cord and testis[J]. Journal of Neuroscience Methods, 2006, 152(1/2):1-9.
[24] Janovitz T, Klein I A, Oliveira T, et al. High-throughput sequencing reveals principles of adeno-associated virus serotype 2 integration[J]. Journal of Virology, 2013, 87(15):855-8568.
[25] Cohn L B, Silva I T, Oliveira T Y, et al. HIV-1 integration landscape during latent and active infection[J]. Cell, 2015, 160(3):420-432.
[26] Xiao J, Zhang L, Wang J, et al. Rearrangement structure-independent strategy of CNV breakpoint analysis[J]. Molecular Genetics and Genomics, 2014, 289(5):755-763.
[27] Du R, Lu C, Jiang Z, et al. Efficient typing of copy number variations in a segmental duplication-mediated rearrangement hotspot using multiplex competitive amplification[J]. Journal of Human Genetics, 2012, 57(8):545-551.
[28] Frye R E, Melnyk S, Macfabe D F. Unique acyl-carnitine profiles are potential biomarkers for acquired mitochondrial disease in autism spectrum disorder[J]. Translational Psychiatry, 2013, 3(1):e220.
[29] Harlow H F. The development of learning in the Rhesus monkey[J]. American Scientist, 1959, 47(4):354A-479.
[30] Ha J C, Mandell D J, Gray J. Two-item discrimination and Hamilton search learning in infant pigtailed macaque monkeys[J]. Behavioural Processes, 2011, 86(1):1-6.
[31] Liu Z, Nie Y H, Zhang C C, et al. Generation of macaques with sperm derived from juvenile monkey testicular xenografts[J]. Cell Research, 2015, 26(1):139-142.