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<p>Impaired social interaction and repetitive behavior are key features observed in individuals with autism spectrum disorder (ASD). <i>SHANK3</i> is a high-confidence ASD risk gene that encodes an abundant scaffolding protein in the postsynaptic density. In wild-type (WT) domestic dogs, maternal behaviors such as licking and nursing (largely milk feeding) of puppies are most commonly observed. To address whether <i>SHANK3</i> plays a role in social behaviors especially maternal behaviors, we analyzed <i>Shank3</i> mutant dogs generated by CRISPR/Cas9 methodology. We found that <i>Shank3</i> mutant dams exhibited a fewer and shorter licking behavior, as well as reduced nursing frequency when compared with WT dams. Additionally, a significant decrease in blood oxytocin (OXT) concentration was detected in <i>Shank3</i> mutant dams. We thus conducted a vehicle-controlled experiment to examine whether a two-week intranasal OXT treatment, initiated on the 8<sup>th</sup> postpartum day, could rescue the maternal licking deficits in <i>Shank3</i> mutant dams. We found that the decreased licking behavior in <i>Shank3</i> mutant dams was significantly attenuated both acutely and chronically by OXT treatment. The rescue effect of OXT implicates an oxytocinergic contribution to the maternal defects in <i>Shank3</i> mutant dams, suggesting a potential therapeutic strategy for <i>SHANK3</i>-associated ASD.</p>

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Oxytocin improves maternal licking behavior deficits in autism-associated Shank3 mutant dogs

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月6日

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  • Wen Lyu,
  • Yuan Li,
  • Aiyu Yao,
  • Qing-quan Tan,
  • Rong Zhang,
  • Jian-ping Zhao,
  • Kun Guo,
  • Yong-hui Jiang,
  • Rui Tian,
  • Yong Q. Zhang

摘要

Impaired social interaction and repetitive behavior are key features observed in individuals with autism spectrum disorder (ASD). SHANK3 is a high-confidence ASD risk gene that encodes an abundant scaffolding protein in the postsynaptic density. In wild-type (WT) domestic dogs, maternal behaviors such as licking and nursing (largely milk feeding) of puppies are most commonly observed. To address whether SHANK3 plays a role in social behaviors especially maternal behaviors, we analyzed Shank3 mutant dogs generated by CRISPR/Cas9 methodology. We found that Shank3 mutant dams exhibited a fewer and shorter licking behavior, as well as reduced nursing frequency when compared with WT dams. Additionally, a significant decrease in blood oxytocin (OXT) concentration was detected in Shank3 mutant dams. We thus conducted a vehicle-controlled experiment to examine whether a two-week intranasal OXT treatment, initiated on the 8th postpartum day, could rescue the maternal licking deficits in Shank3 mutant dams. We found that the decreased licking behavior in Shank3 mutant dams was significantly attenuated both acutely and chronically by OXT treatment. The rescue effect of OXT implicates an oxytocinergic contribution to the maternal defects in Shank3 mutant dams, suggesting a potential therapeutic strategy for SHANK3-associated ASD.