Peripheral Mechanosensory Neuron Dysfunction Underlies Tactile and Behavioral Deficits in Mouse Models of ASDs
Open accessAbstract
Patients with autism spectrum disorders (ASDs) commonly experience aberrant tactile sensitivity, yet the neural alterations underlying somatosensory dysfunction and the extent to which tactile deficits contribute to ASD characteristics are unknown. We report that mice harboring mutations in Mecp2, Gabrb3, Shank3, and Fmr1 genes associated with ASDs in humans exhibit altered tactile discrimination and hypersensitivity to gentle touch. Deletion of Mecp2 or Gabrb3 in peripheral somatosensory neurons causes mechanosensory dysfunction through loss of GABAA receptor-mediated presynaptic inhibition of inputs to the CNS. Remarkably, tactile defects resulting from Mecp2 or Gabrb3 deletion in somatosensory neurons during development, but not in adulthood, cause social interaction deficits and anxiety-like behavior. Restoring Mecp2 expression exclusively in the somatosensory neurons of Mecp2-null mice rescues tactile sensitivity, anxiety-like behavior, and social interaction deficits, but not lethality, memory, or motor deficits. Thus, mechanosensory processing defects contribute to anxiety-like behavior and social interaction deficits in ASD mouse models. PAPERCLIP.
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Individuals with ASD may have heightened sensitivity and preoccupation with self.
“They may also have heightened sensitivity and preoccupation with self 45,46.”
From Reduced sociability and social agency encoding in adult Shank3-mutant mice are restored through gene re-expression in real time (2021) · cites this paper as [45]
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- Authors
- Orefice, L. L., Zimmerman, A. L., Chirila, A. M., Sleboda, S. J., Head, J. P., & Ginty, D. D.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Ginty, David D.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 166
- Issue
- 2
- Pages
- 299-313
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5567792
- OpenAlex
- W2415803194
- Cited by
- 383
- References
- 48
- Citations by year
- 2026: 39 · 2025: 41 · 2024: 34 · 2023: 45 · 2022: 44 · 2021: 45 · 2020: 41 · 2019: 35 · 2018: 20 · 2017: 29 · 2016: 9
- FWCI
- 25.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Neurological Disorders and Stroke (R01NS034814, R37NS034814, R35NS097344, T32NS007484)
- National Institute of Dental and Craniofacial Research (R01DE022750)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Tactile and Sensory Interactions
- Keywords
- autism spectrum disorder, mechanosensory neurons, somatosensory impairment, tactile hypersensitivity, tactile discrimination, MeCP2, GABRB3, SHANK3, FMR1 gene, GABAA receptor, presynaptic inhibition, anxiety-like behavior, social interaction deficits, mouse model
- MeSH terms
- Autism Spectrum Disorder, Animals, Behavior, Animal, Disease Models, Animal, Interpersonal Relations, Receptors, GABA-A, Sensory Receptor Cells, Synapses, Touch, Mice, Methyl-CpG-Binding Protein 2, Spinal Cord Dorsal Horn
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