PX-RICS-deficient mice mimic autism spectrum disorder in Jacobsen syndrome through impaired GABAA receptor trafficking
Copyright policy )PX-RICS-deficient mice mimic autism spectrum disorder in Jacobsen syndrome through impaired GABAA receptor trafficking
AbstractJacobsen syndrome (JBS) is a rare congenital disorder caused by a terminal deletion of the long arm of chromosome 11. A subset of patients exhibit social behavioural problems that meet the diagnostic criteria for autism spectrum disorder (ASD); however, the underlying molecular pathogenesis remains poorly understood. PX-RICS is located in the chromosomal region commonly deleted in JBS patients with autistic-like behaviour. Here we report that PX-RICS-deficient mice exhibit ASD-like social behaviours and ASD-related comorbidities. PX-RICS-deficient neurons show reduced surface γ-aminobutyric acid type A receptor (GABAAR) levels and impaired GABAAR-mediated synaptic transmission. PX-RICS, GABARAP and 14-3-3ζ/θ form an adaptor complex that interconnects GABAAR and dynein/dynactin, thereby facilitating GABAAR surface expression. ASD-like behavioural abnormalities in PX-RICS-deficient mice are ameliorated by enhancing inhibitory synaptic transmission with a GABAAR agonist. Our findings demonstrate a critical role of PX-RICS in cognition and suggest a causal link between PX-RICS deletion and ASD-like behaviour in JBS patients.
- University of California, San Diego United States
- San Diego State University United States
- University of California, San Diego United States
- University of Tokyo Japan
Autism Spectrum Disorder, Science, Article, Clonazepam, Mice, Seizures, Excitatory Amino Acid Agonists, Animals, Jacobsen Distal 11q Deletion Syndrome, GABA Modulators, Social Behavior, Mice, Knockout, Kainic Acid, Behavior, Animal, Q, GTPase-Activating Proteins, Olfactory Perception, Receptors, GABA-A, Grooming, Protein Transport, Stereotyped Behavior, Vocalization, Animal
Autism Spectrum Disorder, Science, Article, Clonazepam, Mice, Seizures, Excitatory Amino Acid Agonists, Animals, Jacobsen Distal 11q Deletion Syndrome, GABA Modulators, Social Behavior, Mice, Knockout, Kainic Acid, Behavior, Animal, Q, GTPase-Activating Proteins, Olfactory Perception, Receptors, GABA-A, Grooming, Protein Transport, Stereotyped Behavior, Vocalization, Animal
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