Behavioral and Cerebellar Transmission Deficits in Mice Lacking the Autism-Linked Gene Islet Brain-2
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Deletion of the human SHANK3 gene near the terminus of chromosome 22q is associated with Phelan–McDermid syndrome and autism spectrum disorders. Nearly all such deletions also span the tightly linked IB2 gene. We show here that IB2 protein is broadly expressed in the brain and is highly enriched within postsynaptic densities. Experimental disruption of the IB2 gene in mice reduces AMPA and enhances NMDA receptor-mediated glutamatergic transmission in cerebellum, changes the morphology of Purkinje cell dendritic arbors, and induces motor and cognitive deficits suggesting an autism phenotype. These findings support a role for human IB2 mutation as a contributing genetic factor in Chr22qter-associated cognitive disorders.
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Behavioral analyses of IB2 and Pax6 animal models indicate a possible link between these genes and autistic-like behavior.
“Behavioral analyses of both IB2 and Pax6 animal models have also indicated a possible link between these genes and autistic-like behavior [277, 279].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [277]
Specific deletion of IB2 in mice causes altered Purkinje cell morphology and disrupted cerebellar glutamatergic transmission.
“Specific deletion of IB2 in mice results in altered Purkinje cell morphology and disruptions in cerebellar glutamatergic transmission [277].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [277]
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- Rossi P Sola E Taglietti V Borchardt T Steigerwald F Utvik JK Ottersen OP Kohr G D'Angelo E 2002b NMDA receptor 2 (NR2) C-terminal control of NR open probability regulates synaptic transmission and plasticity at a cerebellar synapse J Neurosci 22 9687 9697 12427824 PMC6757821
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Consensus Paper: Pathological Role of the Cerebellum in Autism
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- Authors
- Giza, J., Urbanski, M. J., Prestori, F., Bandyopadhyay, B., Yam, A., Friedrich, V., Kelley, K., D'Angelo, E., & Goldfarb, M.
- Affiliations
- City University of New York (US)
- University of Pavia (IT)
- Icahn School of Medicine at Mount Sinai (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-11-03
- Volume
- 30
- Issue
- 44
- Pages
- 14805-14816
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3200367
- OpenAlex
- W1968782484
- Cited by
- 68
- References
- 62
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 7 · 2017: 4 · 2016: 3 · 2015: 4 · 2014: 9 · 2013: 3 · 2012: 5
- FWCI
- 2.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Commission
- National Institute of Neurological Disorders and Stroke (R01NS039906, U54NS041073, U54-NS40173)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- SHANK3, Phelan-McDermid syndrome, autism spectrum disorder, chromosome 22q deletion, postsynaptic density, AMPA receptors, NMDA receptor, glutamatergic neurotransmission, cerebellum, motor impairment, cognitive impairment, mouse model
- MeSH terms
- Animals, Mental Disorders, Cerebellar Diseases, Child Development Disorders, Pervasive, Chromosomes, Human, Pair 22, Cognition Disorders, Disease Models, Animal, Female, Humans, Infant, Newborn, Male, Mice, Transgenic, Synaptic Transmission, Receptors, N-Methyl-D-Aspartate, Receptors, AMPA, Mice, Knockout, Genetic Predisposition to Disease, Adaptor Proteins, Signal Transducing, Mice
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