Chinese scientists have inserted a gene in monkeys that causes an extremely rare autism syndrome in people.
The mutant monkeys show unusual features in their first few years of life, including anxiety, abnormal social interactions, and running in circles around their cages, as described on Monday in the journal Nature.
The monkeys took six years to develop, and their care costs up to 50 times more than laboratory mice, the scientists said. Experiments on monkeys are also more ethically fraught.
But researchers are increasingly disillusioned with mouse models of brain disorders. The vast majority of studies of experimental drugs are done on rodents, and about 90% of those drugs fail when actually tested in people. (Just this month, pharma giant Novartis reported the failure of two clinical trials of a touted autism drug that had reversed symptoms in mouse models.)
“We think this non-human primate is absolutely required, in the long run, for our development of therapies and drugs for human psychiatric and neurological disease,” Mu-ming Poo, director of the Institute of Neuroscience at the Chinese Academy of Sciences in Shanghai, where the new monkey work was carried out, said at a press briefing. “There seems no other choice.”
Autism’s diverse array of social and communication problems is difficult, if not impossible, to fully model in any animal. And the new mutant monkeys diverge from the human syndrome in important ways.
Still, independent scientists told BuzzFeed News that making the monkeys was an impressive technological feat. And these animals — long-tailed macaques — are far closer to us on the evolutionary family tree than mice are.
“For me, it’s not even a question that one should study primates versus mice in this context,” said Partha Mitra, a professor at Cold Spring Harbor Laboratory in New York, who is working on brain-mapping projects in both mice and monkeys.
Genetically engineered monkeys are fairly new. In 2008, scientists at Emory University in Atlanta debuted monkeys carrying the gene for Huntington’s disease. The next year, Japanese researchers made transgenic monkeys that passed on a mutant gene — a jellyfish gene that glows green under UV light — to their offspring.
The Institute of Neuroscience in Shanghai has several groups working on transgenic monkeys, and they share a colony of about 500 animals, Poo said.
In the new study, a team led by the Institute’s Zilong Qiu focused on a rare autism syndrome caused by extra copies of a gene called MECP2. This so-called MECP2 duplication syndrome was first reported in people in 2004, the same year that the disorder was modeled in genetically engineered mice.
The syndrome often includes social problems and anxiety. But, in both people and mouse models, the condition is also characterized by low muscle tone, learning difficulties, and seizures — none of which were reported in the mutant monkeys.
“There are many features of this [monkey model] that are really distinct from the human disorder,” said Huda Zoghbi, whose lab at Baylor College of Medicine in Houston has long studied MECP2 in mice, as well as people with MECP2 duplication syndrome. “I don’t know what to make of the circling behavior — none of the patients I have seen have the circling behavior.”
The differences in the mutant monkeys could be due to when, exactly, the MECP2 gene turns on during development, as well where in the brain, Zoghbi said.
Though these monkey models aren’t yet good mimics of the syndrome, Zoghbi added, they will likely improve over time. And if they do, they could help researchers test experimental drugs.
“Let’s say we discovered a drug that cures the mouse completely,” Zoghbi said. “The big question is, do you go from that mouse straight to human? Or test in a couple of those monkeys first.”
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