January 25, 2016

expert reaction to transgenic monkeys could aid study of autism

Animal models are often used to study disease processes and treatments and a study published in the journal Nature describes one such monkey model which has been used to investigate autism, with the authors reporting that the monkeys displayed autism-like behaviour.

Prof. Roger Lemon, Sobell Chair of Neurophysiology, UCL, said:

“I think this is a potentially very important scientific development. Given the widespread incidence of autism in humans, and some of its debilitating side effects, important clinical insights could also result from this new transgenic model. The model in a non-human primate is justified because autism and many other disorders can best be investigated in a model system as close as possible to that of the human brain; this work will no doubt complement that in rodent and other models. From my reading of the paper, there are also significant welfare issues. These would need to be taken into account in assessing the future of this research programme.”

Dr Payam Rezaie, Reader in Neuropathology, The Open University, said:

“Non-human primate (NHP) models such as this provide unique insight into how the biology of the developing brain relates more closely to ‘human’ behaviours (including social and cognitive function). Dynamic social structures, cognitive and attentional processes, and the structural and functional complexity of neural circuitry in NHP offer invaluable insight at a systems-level that simply cannot be obtained from studies in lower mammals (rodents), or through other experimental means.

“This particular study focuses on the behavioural consequences of overexpressing the human MECP2 gene specifically in the brain. The model is clinically relevant to MECP2 duplication syndrome (MDS), in which affected individuals exhibit some of the characteristic behaviours associated with autism. While the study has limitations (e.g. seizures and gait abnormalities – phenotypes associated with MECP2 duplication syndrome –  were not observed in the transgenic model, a correlation between copy number of transgenes and severity of behavioural changes could not be established, mortality and gender-specific differences need further evaluation, and the sample size was limited to 8), it does represent an important step forward in our ability to understand highly complex neurodevelopmental disorders which involve MECP2, the functional relationship to ‘human’ behaviours associated with autism, and how these may be inherited (passed on through generations).

“The study also paves the way for better understanding of postnatal brain development, gene-environmental interactions and the impact of epigenetic factors on autism-like behaviours. Like humans, NHP also display significant individual variability in the extent of behaviours, including in their social behaviour and interaction. This individual variability, reflected to some degree in this study, can only be partially explained by genetic factors, but is also key to understanding the variability of behaviours associated with autism.

“As with all research involving NHP, ethical considerations, scientific advancement and the impact and potential benefit for treatment that could be gained from experimental research involving NHP, should be carefully considered.”

Dr James Cusack, Research Director, Autistica, said:

“Developing sophisticated animal models of autism has always represented a significant challenge for scientists.  This excellent research has developed a more sophisticated model of autism which may further our understanding of autism, and could eventually lead to the development of more tailored treatments.

“It should always be remembered that people with autism vary in a number of ways, and autism itself is linked to a number of other conditions.  With this in mind, developing a single animal model of autism may be difficult to achieve.”

‘Autism-like behaviours and germline transmission in transgenic monkeys overexpressing MeCP2’ by Liu et al. published in Nature on Monday 25^th January. 

Declared interests

Prof. Lemon: None declared

Dr Rezaie: “I confirm that there are no conflicts of interest in relation to this activity.”

Dr Cusack: None declared