Scientists Genetically Engineer Autistic Monkeys
Scientists in China have genetically altered monkeys to have a human gene associated with autism spectrum disorders. As a result, the monkeys show a range of symptoms associated with autism. Their findings were published today in the journal Nature.
Mutations of methyl-CpG binding protein 2 (MECP2) are found in 90 percent of patients with Rett syndrome, a severe developmental disorder affecting mostly girls that is classified as an autism spectrum disorder. MECP2 duplication syndrome, in which a person has multiple copies of the gene, also shares core symptoms with autism spectrum disorders. It mostly affects boys. The researchers inserted the MECP2 gene into oocytes, or egg cells, of Macaca fascicularis (known variously as the crab-eating macaque or cynomolgus monkey). After fertilization, 53 embryos were then transferred into 18 surrogate monkeys. Half became pregnant, and eight offspring were born.
For the first year the monkeys were developmentally normal, but then issues began to appear. By about 18 months, "the first cohort of transgenic monkeys showed very similar behaviors related to human autism patients, including repetitive behaviors, increased anxiety, and most importantly, defects in social interactions," study co-author Zilong Qiu said in a press-only teleconference on January 21. The monkeys paced in circles around their cages and made a lot of anxious sounds, including grunts and screams.
The researchers then used an "accelerated reproduction method" to produce a second generation of transgenic monkeys, which also showed defects in social interactions.
This genetic inheritance makes these transgenic monkeys "a very unique model for studying human autism," Qiu said.
Scientists generally use mice to study autism, but there are problems with that approach. For one thing, mice lack an area of the brain known as the prefrontal cortex, which is where some psychiatric disorders appear to be centered, MIT Technology Review notes.
"Mouse models have many advantages, such as low cost, the ability to generate large sample sizes and to carry out extensive pilot work quickly," Melissa Bauman, a researcher at the University of California who specializes in animal models of autism, said in a press statement to Nature. "However, given that Autism Spectrum Disorder (ASD) is [a] uniquely human disorder characterized by deficits in complex behaviors, there are limitations in relying solely on mouse models."
Another researcher cautioned that autism is an incredibly complex disease without a single underlying biological cause. "Some cases of autism do derive from relatively simple genetic events. Mutations in MECP2 and the duplication of MECP2 are only one of these myriad causes," said University of Mississippi Medical Center researcher Eric Vallender in another press statement. Vallender, who studies the neurogenetics of nonhuman primates (NHP), also noted that "repetitive motor behaviors and anxiety-like behaviors can be caused by many things, and 'decreased social interaction' is always tricky to both observe and quantify and to interpret.
"That said," he added, "they have created an excellent model of MECP2 duplication syndrome. This is not trivial and can be a major step forward for understanding neurodevelopmental disorders."
The researchers are currently conducting brain imaging studies of the MECP2 monkeys to try to identify the deficiency in the brain circuits that is responsible for autism-like behavior. Once they identify this brain circuit, they'll attempt to treat the monkeys using various methods, including more genetic modification: "We will use therapeutics, such as gene-editing tools like CRISPR-Cas9 … to explore the potential gene therapy," Qiu said.
Meanwhile, the creation of transgenic NHPs raises ethical questions, as University of Toronto bioethicist Kerry Bowman told Gizmodo: “Transgenic NHP will potentially exhibit traits that are the most human-like; in turn this puts them at greater risk of research exploitation.”