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Publication
Autism-associated gene shank3 is necessary for social contagion in zebrafish
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Advisor(s)
Abstract(s)
Background Animal models enable targeting autism-associated genes, such as the shank3 gene, to assess their
impact on behavioural phenotypes. However, this is often limited to simple behaviours relevant for social interaction.
Social contagion is a complex phenotype forming the basis of human empathic behaviour and involves attention
to the behaviour of others for recognizing and sharing their emotional or affective state. Thus, it is a form of social
communication, which constitutes the most common developmental impairment across autism spectrum disorders
(ASD).
Methods Here we describe the development of a zebrafish model that identifies the neurocognitive mechanisms by
which shank3 mutation drives deficits in social contagion. We used a CRISPR-Cas9 technique to generate mutations
to the shank3a gene, a zebrafish paralogue found to present greater orthology and functional conservation relative to
the human gene. Mutants were first compared to wild types during a two-phase protocol that involves the observation
of two conflicting states, distress and neutral, and the later recall and discrimination of others when no longer
presenting such differences. Then, the whole-brain expression of different neuroplasticity markers was compared
between genotypes and their contribution to cluster-specific phenotypic variation was assessed.
Results The shank3 mutation markedly reduced social contagion via deficits in attention contributing to difficulties
in recognising affective states. Also, the mutation changed the expression of neuronal plasticity genes. However, only
downregulated neuroligins clustered with shank3a expression under a combined synaptogenesis component that
contributed specifically to variation in attention.
Limitations While zebrafish are extremely useful in identifying the role of shank3 mutations to composite social
behaviour, they are unlikely to represent the full complexity of socio-cognitive and communication deficits presented
by human ASD pathology. Moreover, zebrafish cannot represent the scaling up of these deficits to higher-order
empathic and prosocial phenotypes seen in humans.
Conclusions We demonstrate a causal link between the zebrafish orthologue of an ASD-associated gene and the
attentional control of affect recognition and consequent social contagion. This models autistic affect-communication
pathology in zebrafish and reveals a genetic attention-deficit mechanism, addressing the ongoing debate for such
mechanisms accounting for emotion recognition difficulties in autistic individuals.
Description
Keywords
Autism SHANK3 Social contagion Zebrafish, Affect Recognition Attention Neuroplasticity Synaptogenesis Neuroligins
Citation
Kareklas, K., Teles, M. C., Dreosti, E., & Oliveira, R. F. (2023). Autism-associated gene shank3 is necessary for social contagion in zebrafish. Molecular Autism, 14(1), 1–15. https://doi.org/10.1186/s13229-023-00555-4
Publisher
BioMed Central Ltd.