A macaque model for autism

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Much like autistic children, these macaques follow repetitive rituals. Much like autistic children, they become anxious in response to eye contact and vocally express their distress. And much like autistic children, they avoid social interactions with their peers. These macaques are the first non-human primate model for autism spectrum disorders (ASDs), specifically the Rett Syndrome.

Generated by a team of scientists led by Zilong Qiu and Qiang Sun from Shanghai Institutes for Biological Sciences and Fudan University in China, these ‘autistic monkeys’ have been genetically engineered to overexpress a Rett syndrome-associated human gene MeCP2—90% of patients with Rett syndrome have mutations in the MECP2 gene— in their brains. Tweaking monkey genes is quite daunting a task, but the team hacked through this hurdle by using of a gene-editing system called TALENS that makes use of a DNA-binding protein from bacteria that infect plants to ‘infect’ DNA with the gene of interest. Importantly, the team has not only created autistic monkeys, but also proved germline transmission of autistic traits. This is to say that it is not only these monkeys that are autistic, but also their present and/or future progeny. A group of scientists from China had previously developed a monkey model for RS, but this is the first study to link the gene to behavioral deficits and demonstrate that the disorder can be transferred from the parent to their children.

It is important to acknowledge the sheer necessity of creating such an autistic primate model system. These monkeys offer a unique lens through which we can peer into the biology of autism and investigate new test treatments for this spectrum of disorders. Thus far, we have relied on genetic models of ASD in rodents to discover the various molecular characters that play out autism. However, the differences in brain anatomy and their sheer lack of cognitive and behavioral complexity limit the impact of rodents on understanding ASDs to basic mechanisms. ASDs are a complex set of behavioral and social disorders and in order to understand their molecular plot-line and tease apart the role every molecular character plays in bringing forth the behavioral manifestations of ASDs, a primate model is absolutely essential.

These monkeys appear to mirror a variety of the traits of Rett syndrome. And even if all the ASD symptomology cannot be modeled, the primate model system has the distinct advantage of good correlation with human behavior—refer to teenagers for proof-of-concept. We share much of our complex social behaviour and brain anatomy with our closest cousins. Having a primate model for the disorder provides us a unique opportunity to better address the pathology of Rett Syndrome, perhaps even test if genetic engineering can be used to optimise gene expression. In short, we are trying to say, exciting days ahead!

Original Article: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature16533.html

Link to video: https://www.youtube.com/watch?v=yMtLs2PGMXM

Artwork: Leslee Lazar