Dogs

Reduced attention to human eyes in autism-associated Shank3 mutant laboratory beagle dogs

Abstract

Autistic individuals often exhibit reduced attention to faces and eyes, which may underlie their social difficulty. This study used eye-tracking techniques to explore visual attention towards faces in Shank3 mutant laboratory beagle dogs, a model for autism, to identify parallels with human autism. We first assessed visual attention differences towards the eyes between Shank3 mutant and wild-type (WT) laboratory beagles by presenting them with human and dog face images. Then, using the gaze cueing paradigm, we directed the dogs’ gaze towards the eyes and mouth and quantified their gaze shifts. Finally, we investigated the impact of oxytocin on eye-gaze behavior by comparing gaze patterns under pre-administration, vehicle, and oxytocin conditions while viewing human faces. We found that mutant dogs showed a reduced proportional viewing time of human eyes than WT dogs (p = 0.032), but no difference in proportional eye viewing time when viewing dog faces (p = 0.691). Mutant dogs shifted their gazes away from the human eyes more quickly than the mouth (p = 0.043), unlike WT dogs (p = 0.345), suggesting an active eye avoidance. Furthermore, exogenous oxytocin increased proportional viewing time on human eyes in mutant dogs than pre-administration and vehicle conditions (p = 0.022), suggesting a potential effect of oxytocin on social attention in autism. To our knowledge, this study is the first to report an eye avoidance phenotype in an animal model of autism. These findings contribute to our understanding of the mechanisms underlying social difficulties in autism and the development of supporting strategies for autism.



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Fig. 1: Design of an eye-tracking system for dogs.
Fig. 2: Shank3 mutant dogs showed a reduced proportional viewing time in the eye region of human faces.
Fig. 3: Shank3 mutant dogs showed a typical proportional viewing time in the eye region of dog faces.
Fig. 4: Shank3 mutant dogs shifted away from the eye region more quickly than the mouth region.
Fig. 5: Nasal spray of oxytocin increased the proportional viewing time in the human eye region in Shank3 mutant dogs.

Data availability

The datasets generated and analyzed during the current study are available from the corresponding author upon request.

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Acknowledgements

This work was supported in part by by grants from the National Key Research and Development Program (2021ZD0203901 to Y.Q.Z.), the National Natural Science Foundation of China (32394030 to Y.Q.Z., 32200872 to Q.D.W., and 32271116 to L.Y.), Wuhan Municipal S&T Project (Grant No. 2024020702030125 to Y.Q.Z.), and the Canine Biobank, Chinese Academy of Sciences (KFJ-BRP-004 to Y.Q.Z.).

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Author notes

  1. These authors contributed equally: Yumo Li, Qiandong Wang.

Authors and Affiliations

  1. State Key Laboratory for Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China

    Yumo Li, Siqi Yuan & Yong Q. Zhang

  2. College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China

    Yumo Li, Siqi Yuan & Yong Q. Zhang

  3. Beijing Key Laboratory of Applied Experimental Psychology, National Demonstration Center for Experimental Psychology Education, Faculty of Psychology, Beijing Normal University, Beijing, China

    Qiandong Wang & Tak Kwan Lam

  4. Education Research Center for Children with ASD, Beijing Normal University, Beijing, China

    Qiandong Wang

  5. School of Psychology, University of Lincoln, Brayford Pool, Lincoln, LN6 7TS, UK

    Kun Guo

  6. School of Life Sciences, Hubei University, Wuhan, China

    Yong Q. Zhang

  7. School of Psychological and Cognitive Sciences & Beijing Key Laboratory of Behavior and Mental Health, Peking University, Beijing, China

    Li Yi

  8. IDG/McGovern Institute for Brain Research at PKU, Peking University, Beijing, China

    Li Yi

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Contributions

LY and YQZ conceptualized the project, supervised data collection and analysis. YML, QDW and SQY designed and performed experiments. YML, QDW and LTK completed data collection and analysis. YML, QDW, LY, and YQZ wrote the manuscript, and KG, LY, and YQZ finalized the manuscript. YML and QDW contributed equally to this work as first contributing authors. LY and YQZ contributed equally to this work as supervisors.

Corresponding authors

Correspondence to
Yong Q. Zhang or Li Yi.

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The authors declare no competing interests.

Ethics approval and consent to participate

This study was conducted in full compliance with established guidelines for animal experimentation and received ethical approval from the Ethics Committee of the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences (AP2022001).

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41380_2025_2965_MOESM1_ESM.pdf

Supplementary figure 1 (Fig.S1), Supplementary figure 2 (Fig.S2), Supplementary table 1 (Table S1), Supplementary table 2 (Table S2)

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Li, Y., Wang, Q., Yuan, S. et al. Reduced attention to human eyes in autism-associated Shank3 mutant laboratory beagle dogs.
Mol Psychiatry (2025). https://doi.org/10.1038/s41380-025-02965-7

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