Gene editor CRISPR finds "domestic" autistic monkey model

DOI: 10.1038/s41586-019-
1278-0 Recently, the Shenzhen Institute of Advanced Technology of the Chinese Academy of Sciences, Zhou Wei, Sun Yat-sen University, Yang Shihua of South China Agricultural University and Professor Robert Desimone Feng Guoping of the Massachusetts Institute of Technology jointly published a paper in the international leading journal Nature, in the development of autistic non-human primate models to achieve new breakthroughsresearchers successfully modified the Shank3 gene, which is highly associated with autism, on macaques using the CRISPR gene editing systemThe absence or mutation of the gene can lead to immature brain neurons, reduced neural connections, and individuals exhibit autism symptoms such as social avoidance and stereotyped behaviorautism and genetic variationscientists have discovered hundreds of genetic variants associated with autism, many of which pose only a small riskFor the study, the researchers focused on a highly correlated gene, Shank3Shank3-coded protein is present in synapses that connect brain cells, and Shank3's role is to allow brain cells to communicate with each otherProfessor Feng and his colleagues have previously studied mice with shank3 gene mutations and found that they exhibited a number of autism-related traits, including avoiding social and compulsive repetitive behaviorsIn addition to being associated with autism, Shank3 mutations or deletions can also lead to a related rare disease, the most common characteristics of which include intellectual impairment, impaired speech and sleep, and repetitive behaviorProfessor Feng Guoping,, said: "Although mouse studies can provide a great deal of information about the molecular basis of disease, there are drawbacks in using them to study neurodevelopmental disordersIn particular, mice lacked a highly developed prefrontal cortex, which is home to the unique characteristics of many primates, such as decision-making, staying focused, and interpreting social cues, which are often affected by brain disorders"Why didchoose macaques? Robert Desimone, director of the McGovern Brain Institute at the Massachusetts Institute of, said: "We urgently need new treatments to treat autism spectrum disorders, but previous treatments developed in mice are not satisfactoryWhile research in mice is also important, we believe that primate genetic models will help us develop better drugs and even apply gene therapy to some severe autism it is worth mentioning that the director of the Institute of Neuroscience of the Chinese Academy of Sciences, Professor Pu Muming, has also said that the reason for choosing primates (macaques) as an animal model of brain science is mainly based on two points The first is that primates have higher cognitive abilities that mice do not have another important reason is that the rhythm of life of macaques is very similar to people, if you knock out the monkey rhythm gene, you can find that it has many symptoms can reflect the abnormal rhythm of people, such as abnormal sleep, anxiety, depression, and even some symptoms of schizophrenia CRISPR helped find a model of autistic macaques
researchers injected CRISPR components into the fertilized eggs of macaques and successfully produced macaques with the shank3 mutation through surrogacy monkeys analysis found that mutant macaques exhibited behavioral characteristics similar to those in people with autism, such as sleep disorders, increased repetitive stereotypes, and decreased social interaction In social stimulation, mutant monkeys exhibit abnormal eye movement patterns and pupil responses over a long incubation period, which are highly consistent with those of people with autism Shank3-Mutant Macaques have a whole and local connection disorder
MRI scans further revealed patterns similar to those of human autism spectrum disorders in mutant monkeys The structure shows the decrease of gray matter volume, the function shows the long-range connection between the brain interval (e.g the back buckle and the inner frontal lobe) is reduced, and the local connection is enhanced this study demonstrates the successful establishment of a new model of genetically modified autism primates, providing a better research basis for a deeper understanding of the neurobiological mechanisms of autism and the development of more transformative treatments references: s1 s 1 , Using Gene editing, neuros develop a new model for autism .