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NEURODEVELOPMENTAL DISORDERS

Sex bias in autism: new insights from Chd8 mutant mice?

Nature Neuroscience volume 21, pages 1144–1146 (2018)Cite this article

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A study has found that young male mice with a mutation of the autism-associated gene Chd8 show abnormal behaviors and elevated neuronal activation in several brain areas under stressful conditions, while female mice with the same mutation have reduced baseline neuronal activity, which may protect them from developing these abnormal phenotypes.

Do autism-related genes affect girls differently from boys? Approximately three to four times more boys are diagnosed with autism spectrum disorder (ASD) than girls1. Clinicians and scientists have pondered the reason for this striking sex effect for many years, and a number of different explanations have been offered. One model that is receiving some traction proposes that females are somehow more ‘resistant’ to ASD. There is also a growing realization that ASD may manifest in different ways in females and males, with important diagnostic implications1. Human genetic studies have found clear evidence that females are somehow more resilient to even highly penetrant ASD-associated mutations2. One possible model proposes that neuronal activation in specific brain regions may be different in male and female ASD subjects. For example, Beacher et al. reported reduced activation of brain regions in females during a mental rotation task, while males showed hyperactivation in the same task3, but, as with most studies of its kind, the underlying genetic cause of autism in the subjects under investigation was not known. Can the analysis of mouse models with defined autism-linked mutations and genetic backgrounds provide transformative insights into the developmental and neuronal basis of the sex bias in autism?

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Fig. 1: Sex differences in Chd8+/− mice.

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Authors and Affiliations

  1. MRC Centre for Neurodevelopmental Disorders, King’s College London, London, UK

    Laura C. Andreae & M. Albert Basson

  2. Centre for Developmental Neurobiology, King’s College London, London, UK

    Laura C. Andreae

  3. Centre for Craniofacial and Regenerative Biology, King’s College London, London, UK

    M. Albert Basson

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  1. Laura C. Andreae
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  2. M. Albert Basson
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Correspondence to M. Albert Basson.

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Andreae, L.C., Basson, M.A. Sex bias in autism: new insights from Chd8 mutant mice?. Nat Neurosci 21, 1144–1146 (2018). https://doi.org/10.1038/s41593-018-0217-y

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