Genetically Modified Monkeys Might Aid Autism Research

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Chinese scientists report they’ve created monkeys that carry a gene linked to autism-like behaviors.

The altered monkeys also produced offspring that inherited the human gene, according to research published online Jan. 25 in the journal Nature.

The so-called “transgenic” monkeys provide a “very unique model for studying human autism,” study co-author Zilong Qiu, of the Institute of Neuroscience at the Chinese Academy of Science in Shanghai, told reporters at a news briefing to announce the findings.

Currently, gene-altered mice are widely used to model human genetic conditions, but scientists cite obvious limitations.

The question is “whether we can mimic the complicated symptoms” of human autism patients in a mouse, explained Qiu.

The hope is that developing better animal models — such as monkeys — may lead to important new autism therapies for people.

“This takes us one step closer to having better tools to understand the biological and genetic underpinnings of the signs and symptoms of autism,” said Daniel Smith, vice president of innovative technologies at Autism Speaks, in Boston.

“But, it’s still a tool on that long road to discovering new medicines and interventions,” he added.

One in 160 children globally has autism spectrum disorder, a cluster of complex brain-development disorders in which symptoms include repetitive movements and problems with social interaction. As many as one in 68 children in the United States is believed to be on the autism spectrum, according to the U.S. Centers for Disease Control and Prevention.

To find a better animal model of autism, Chinese researchers generated monkeys that “overexpress” the human gene, known as MECP2. In humans, having too much MECP2 leads to a condition called MECP2 duplication syndrome, which shares core symptoms with autism spectrum disorder.

The research team injected macaque monkey eggs with a virus carrying MECP2. Once fertilized, the resulting embryos were transferred to surrogate monkeys, yielding eight live births. All of the monkeys carried the human gene.

While the monkeys’ mental abilities appeared largely normal, their behaviors did not. Normally, monkeys sit together and groom each other, but the transgenic monkeys in the study were less socially engaged. They also moved about more frequently in repetitive, circular motions. And, they exhibited increased levels of anxiety when faced by a human, as if they were “trying to defend their territory more,” Qiu said.

The researchers also showed that the gene could be passed along to the next generation, a step toward creating colonies of transgenic monkeys for research. Five offspring of one of the genetically altered male monkeys carried the human gene, and those baby monkeys were less social than wild monkeys of a similar age, the study authors said.

MECP2 could be useful in illuminating brain pathways that impact autism patients’ intellectual and cognitive (mental) function, “but it’s not perfect, either,” Smith said. For example, the gene-altered monkeys did not have seizures, a key feature of MECP2 duplication syndrome, he said.

People with autism have a higher-than-average risk of epilepsy, according to the U.S. National Institute of Neurological Disorders and Stroke.

Currently, Qiu said, the Chinese team is using brain imaging to try to identify the brain circuits responsible for the autism-like behavior. Once the target areas are identified, the researchers intend to use a powerful new gene-editing tool, called CRISPR/Cas9, to manipulate the gene and explore potential therapies.

Maintaining monkeys for research is more expensive than housing and feeding rodents, Mu-ming Poo, director of the Institute of Neuroscience in Shanghai, acknowledged during the news briefing. He added that estimates of the costs of using the monkeys are not yet available.

U.S. labs using non-human primates are the exception, not the rule, experts said.

“It’s so expensive here, so I think it’s very tough to do this,” said Rudolf Jaenisch, a founding member of the Whitehead Institute for Biomedical Research, in Cambridge, Mass. Jaenisch is a pioneer in the field of transgenic science, in which researchers alter the genetic makeup of animals.

Primate models, being more human-like than mice, also raise ethical questions.

Poo said the use and care of animals met the Shanghai-based Institute of Neuroscience protocols, which “are exactly the same as an NIH [U.S. National Institutes of Health] protocol.”

Asked for comment on the paper, the NIH said in a statement that it “has supported the development of transgenic non-human primates as early as 2001.”

More information

Visit the U.S. National Institutes of Health for more on autism spectrum disorders.

Source: HealthDay

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