Led by a team from the Institute of Neuroscience at the Chinese Academy of Sciences in Shanghai, researchers have genetically modified monkeys to feature a gene associated with autism spectrum disorder in people, resulting in the most realistic animal model for the condition yet.
Detailing their work in a study published in the journal Nature, the researchers believe that a minimum of 100 genes play a role in the types and symptoms related to autism, which affects one in 45 kids today. Specifically, they turned to MECP2, a gene that people with autism symptoms have extra copies of. This isn't the first time autism-related genes have been engineered into monkeys, but the study is the first to show that there is a link between the genes and how the animals behaved.
The creation of the first batch of genetically modified monkeys occurred in 2010, with MECP2 genes being attached to a dormant virus, which was then injected into the eggs of crab-eating macaque monkeys. After the eggs were fertilized, they were implanted into female monkeys to develop.
This resulted into eight genetically modifed monkeys with one to seven extra copies of the MECP2 gene. Stillborn monkeys were also examined and the researchers found that the gene was also expressed in extra copies in their brains.
Next, the researchers observed a year later that the monkeys involved in the study were showing behaviors hinting at autism. Further tests proved that all of the monkeys were exhibiting at least one symptom related to autism, but this was not enough to say that monkeys were sound autism models.
"We needed to show where the gene makes a difference," said Zilong Qiu, a co-author of the study.
The researchers finally got their opportunity in the next generation of monkeys they genetically modified. The resulting offspring started showing asocial behavior when they were about 11 months old, proving that the MECP2 gene and autism symptoms were passed on to the second-generation macaques in the lab.
Mouse models exist but the macaque model is superior because it actually offers proof that autism-like behaviors are present in animals, although exhibited symptoms are still less severe compared to what human patients have.
For the next phase of their study, the researchers are using brain-imaging technology to pinpoint areas where an overexpression of the gene MECP2 causes trouble. They will then use gene-editing technique CRISPR to remove the extra copies of the gene in the affected region of the brain to see if autism-like symptoms will cease.
In partnership with a mental health hospital, the researchers are also looking to identify which genes linked to autism are most common in the Chinese population.
