28 January 2016

Autistic Macaques

The Chinese have bred monkeys with autism

Oleg Lischuk, N+1 

Chinese scientists have caused a congenital disease in monkeys, similar to one of the forms of autism in humans. To do this, they embedded a human gene in the DNA of animals. A report on their work (Liu et al., Autism-like behaviours and germline transmission in transgenic monkeys overexpressing MeCP2) is published in Nature. 

The research team, led by the staff of the Institute of Neurobiology of the Chinese Academy of Sciences in Shanghai, used crab-eating macaques (Macaca fascicularis) in their work. In the genome of these monkeys, the researchers embedded a protein gene (MECP2) that binds to methylated nucleotides of CpG, type 2. This protein plays an important role in the regulation of transcription and synthesis of microRNAs, it is necessary for the normal functioning of nerve cells.

People with extra copies (MECP2 duplication syndrome) or certain mutations (Rett syndrome) of the MECP2 gene have mental retardation, seizures and symptoms of autism such as repetitive behavior, narrow circle of interests and socialization disorders.

The researchers made sure that in all transgenic animals, additional copies of the MECP2 gene are expressed in the brain. When they reached about one year of age, the monkeys began to show symptoms similar to the manifestations of autism in humans.

In particular, they had repetitive behavior – they ran in a circle for a long time without changing the trajectory. When looking into the eyes, the animals showed a stronger anxiety and stress reaction (anxiety, grumbling, screeching) than ordinary macaques. In addition, they interacted much less with each other and genetically unchanged animals, which indicates impaired socialization.

At the same time, the mental abilities of transgenic monkeys were generally normal, although some animals had stereotypical behavior when learning new information. As in people with MECP2 duplication syndrome, the symptoms were more pronounced in males.


Transgenic macaque. A snapshot from the article Chinese Scientists Created Monkeys Carrying Autism-Related Gene
published on the website of the Chinese Academy of Sciences – VM.

To confirm the effect of genes on the development of symptoms, scientists bred the offspring of experimental macaques. In order not to wait for their puberty, at the age of 27 months, testicular tissue was taken from males and placed under the skin of castrated mice for accelerated maturation. The resulting sperm was used for artificial insemination of eggs of healthy crab-eating macaques.

The MECP2 genes were passed on to the descendants of transgenic monkeys. At about 11 months of life, they developed autism symptoms similar to those of their parents. Such inheritance of genes and phenotype confirmed the validity of the autism model.

The authors of the work hope to use this model to clarify the mechanisms of development and neuroanatomy of the disease, as well as to test various methods of treating autism, including deep electrical stimulation of the brain and genome editing in order to remove the pathological gene.

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