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Chinese researchers have genetically engineered monkeys to carry a human gene linked to autism spectrum disorders. These primates exhibit various behaviors and symptoms characteristic of autism. The study was released today in the prestigious journal Nature.
Mutations in the methyl-CpG binding protein 2 (MECP2) gene are present in 90% of individuals with Rett syndrome, a serious developmental condition primarily impacting girls and categorized under autism spectrum disorders. Similarly, MECP2 duplication syndrome, involving extra copies of the gene, also exhibits core autism-like symptoms and mainly affects males. The team introduced the MECP2 gene into the egg cells of Macaca fascicularis (commonly called crab-eating macaques or cynomolgus monkeys). Following fertilization, 53 embryos were implanted into 18 surrogate mothers. Half achieved pregnancy, resulting in the birth of eight offspring.
Initially, the monkeys developed normally, but after a year, behavioral issues emerged. By around 18 months, "the first group of genetically altered monkeys displayed behaviors akin to those seen in human autism patients, such as repetitive actions, heightened anxiety, and notably, impaired social interactions," explained study co-author Zilong Qiu during a press teleconference on January 21. The monkeys exhibited repetitive circling in their cages and produced frequent anxious vocalizations, including grunts and screams.
The team employed an "accelerated reproduction technique" to create a second generation of genetically modified monkeys, which similarly exhibited impairments in social interactions.
According to Qiu, this genetic trait makes these transgenic monkeys "an exceptional model for investigating human autism."
While mice are commonly used in autism research, this method has limitations. For instance, mice do not possess a prefrontal cortex, a brain region implicated in certain psychiatric conditions, as highlighted by MIT Technology Review.
"Mouse models offer several benefits, including affordability, the capacity to produce large sample sizes, and the ability to conduct preliminary studies rapidly," stated Melissa Bauman, a University of California researcher focused on autism animal models, in a press release to Nature. "However, since Autism Spectrum Disorder (ASD) is a uniquely human condition marked by impairments in complex behaviors, relying exclusively on mouse models has its drawbacks."
Another expert emphasized the complexity of autism, noting it lacks a single biological cause. "While some autism cases stem from straightforward genetic alterations, such as MECP2 mutations or duplications, these represent only a fraction of the potential causes," explained Eric Vallender, a researcher at the University of Mississippi Medical Center, in a separate press statement. Vallender, who specializes in nonhuman primate neurogenetics, added that "repetitive motor actions and anxiety-like behaviors can arise from numerous factors, and assessing 'reduced social interaction' is often challenging to measure and interpret."
"Nevertheless," he continued, "they have developed a remarkable model of MECP2 duplication syndrome. This achievement is significant and could represent a substantial advancement in comprehending neurodevelopmental disorders."
The team is now performing brain imaging analyses on the MECP2 monkeys to pinpoint the specific brain circuit deficiencies linked to autism-like behaviors. Once identified, they plan to explore treatments, including advanced genetic techniques: "We will employ therapeutic approaches, such as CRISPR-Cas9 gene-editing tools, to investigate potential gene therapies," Qiu explained.
At the same time, the development of transgenic nonhuman primates (NHPs) has sparked ethical concerns. As University of Toronto bioethicist Kerry Bowman stated to Gizmodo: "Transgenic NHPs may display traits that closely resemble humans, increasing their vulnerability to exploitation in research."
