Autism, a complex set of brain disorders of social interaction and communication, has been widely studied in lab animals — but most of the research has been in mice, whose brains are very different from those of people.
Now, for the first time, a team of scientists in China has created monkeys whose DNA has been genetically altered to make them develop an autism-like disorder.
These “transgenic” monkeys could be a good model for studying human brain disorders, since their brain circuitry is much closer to that of our own, the authors reported in a study published Monday in the journal Nature.
Autism often involves repetitive behaviours and problems with social interaction. In Rett Syndrome, a rare genetic disorder that causes many of the symptoms of autism, about 90% of patients have a mutation in a gene called MeCP2, which codes for a protein involved in regulating how DNA gets processed to make other proteins. Duplicate copies of this gene produce an autism-like disorder known as MeCP2 duplication syndrome.
Scientists have previously studied this syndrome in mice, and while these animals show many of the developmental and behavioural problems as humans with Rett Syndrome, it’s been harder to study autistic behaviours in rodents, since their brains are so much simpler than a human’s.
Genetically modified monkeys
In the new study, scientists at China’s Shanghai Institutes for Biological Sciences attempted to mimic this disorder in monkeys, which could be a major step toward understanding and treating it in people.
“Once we know the brain circuits responsible, we can start intervening” in these disorders, for example, using noninvasive brain stimulation or gene therapy (a treatment that involves replacing missing or defective genes), study author Zilong Qiu said in a conference in a conference call with reporters last Thursday.
To create the transgenic monkeys, Qiu and his colleagues injected a virus containing multiple copies of the MeCP2 gene into the undeveloped eggs of macaque monkeys, fertilised the eggs, and implanted the 53 resulting embryos into 18 female surrogate monkeys. Nine of the animals got pregnant and three males and five females were born live. Four were stillborn. All of the babies had the duplicate MeCP2 gene.
In a second experiment, they injected 105 embryos into 36 surrogate mothers. Just seven monkeys ended up giving birth to nine babies, but only two survived.
The transgenic monkeys engaged in repetitive motions such as walking in circles, spent less time than normal sitting and interacting with the other monkeys, and showed signs of anxiety — all behaviours that are hallmarks of autistic disorders.
The modified primates didn’t appear to be less intelligent compared with the unmodified animals, but they did show some abnormalities, such as a preference for reaching toward one side when presented with a reward.
To see if the transgenic monkeys could pass on the genetic defect to their offspring, the researchers used sperm from one of the transgenic monkeys to fertilize eggs and implant them into 22 surrogate females. All five monkeys that were born (including one stillborn) carried the MeCP2 mutation, and showed the same deficits in social interaction as their transgenic parent.
The study demonstrated that genetically engineered monkeys can be an effective model for studying autism related disorders and other psychiatric illnesses that are difficult to mimic in simpler animals.
The limits of primate models
Huda Zoghbi, a professor at Baylor College of Medicine who was not involved with the study but who has studied the MeCP2 duplication syndrome in mice, told Business Insider we should be cautious about calling these transgenic monkeys a true model for the disorder, however, because the genes they modified didn’t exactly mirror the effects of the human version of the disease, such as cognitive problems and seizures.
“We need to develop criteria before generating a non-human primate model so that the model is as optimal as possible and it can be useful for preclinical research,” Zoghbi said in an email.
What’s more, monkeys don’t come cheap.
The study researchers said it was hard to give an exact cost figure, since these experiments require hundreds of monkeys across multiple institutions. But raising one monkey in China costs about $3000, and maintaining a monkey facility costs between $500,000 and $1 million per year, they said.
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