ArticleMolecular psychiatry2023
Modeling SHANK3-associated autism spectrum disorder in Beagle dogs via CRISPR/Cas9 gene editing.
Article in Molecular psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Behavioral Convergence with Physiological Divergence: Sex Differences in Hormones but Not Social Behavior in Beagle Dogs.Animals : an open access journal from MDPI · 2026Article
- GWAS for behavioral traits in golden retrievers identifies genes implicated in human temperament, mental health, and cognition.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Autism Spectrum Disorder: The Cerebellum, Genes, and Pathways.Neurology international · 2025Review
- Addictive-like behavioural traits in pet dogs with extreme motivation for toy play.Scientific reports · 2025Article
- Neural mechanisms underlying reduced nocifensive sensitivity in autism-associated Shank3 mutant dogs.Molecular psychiatry · 2025Article
- Review
- Anterior cingulate cortex parvalbumin and somatostatin interneurons shape social behavior in male mice.Nature communications · 2025Article
- Autism-like atypical face processing inScience advances · 2025Article
- Oxytocin improves maternal licking behavior deficits in autism-associated Shank3 mutant dogs.Translational psychiatry · 2025Article
- VDGE: a data repository of variation database for gene-edited animals across multiple species.Nucleic acids research · 2025Article
- Segmentation tracking and clustering system enables accurate multi-animal tracking of social behaviors.Patterns (New York, N.Y.) · 2024Article
- Disrupted Human-Dog Interbrain Neural Coupling in Autism-Associated Shank3 Mutant Dogs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Large-scale genomic analysis of the domestic dog informs biological discovery.Genome research · 2024Review
- Transcriptional determinism and stochasticity contribute to the complexity of autism-associated SHANK family genes.Cell reports · 2024Article
- Transcriptional Determinism and Stochasticity Contribute to the Complexity of Autism AssociatedbioRxiv : the preprint server for biology · 2024Article
- Impaired synaptic function and hyperexcitability of the pyramidal neurons in the prefrontal cortex of autism-associated Shank3 mutant dogs.Molecular autism · 2024Article
- Five cluster classifications of long COVID and their background factors: A cross-sectional study in Japan.Clinical and experimental medicine · 2023Article
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite intensive studies in modeling neuropsychiatric disorders especially autism spectrum disorder (ASD) in animals, many challenges remain. Genetic mutant mice have contributed substantially to the current understanding of the molecular and neural circuit mechanisms underlying ASD. However, the translational value of ASD mouse models in preclinical studies is limited to certain aspects of the disease due to the apparent differences in brain and behavior between rodents and humans. Non-human primates have been used to model ASD in recent years. However, a low reproduction rate due to a long reproductive cycle and a single birth per pregnancy, and an extremely high cost prohibit a wide use of them in preclinical studies. Canine model is an appealing alternative because of its complex and effective dog-human social interactions. In contrast to non-human primates, dog has comparable drug metabolism as humans and a high reproduction rate. In this study, we aimed to model ASD in experimental dogs by manipulating the Shank3 gene as SHANK3 mutations are one of most replicated genetic defects identified from ASD patients. Using CRISPR/Cas9 gene editing, we successfully generated and characterized multiple lines of Beagle Shank3 (bShank3) mutants that have been propagated for a few generations. We developed and validated a battery of behavioral assays that can be used in controlled experimental setting for mutant dogs. bShank3 mutants exhibited distinct and robust social behavior deficits including social withdrawal and reduced social interactions with humans, and heightened anxiety in different experimental settings (n = 27 for wild-type controls and n = 44 for mutants). We demonstrate the feasibility of producing a large number of mutant animals in a reasonable time frame. The robust and unique behavioral findings support the validity and value of a canine model to investigate the pathophysiology and develop treatments for ASD and potentially other psychiatric disorders.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.