The DOI matches its Crossref record; 76 of the 76 references it cites were found in a registry or an index.
Autism gene variant causes hyperserotonemia, serotonin receptor hypersensitivity, social impairment and repetitive behavior
Open accessAbstract
Fifty years ago, increased whole-blood serotonin levels, or hyperserotonemia, first linked disrupted 5-HT homeostasis to Autism Spectrum Disorders (ASDs). The 5-HT transporter (SERT) gene ( SLC6A4 ) has been associated with whole blood 5-HT levels and ASD susceptibility. Previously, we identified multiple gain-of-function SERT coding variants in children with ASD. Here we establish that transgenic mice expressing the most common of these variants, SERT Ala56, exhibit elevated, p38 MAPK-dependent transporter phosphorylation, enhanced 5-HT clearance rates and hyperserotonemia. These effects are accompanied by altered basal firing of raphe 5-HT neurons, as well as 5HT 1A and 5HT 2A receptor hypersensitivity. Strikingly, SERT Ala56 mice display alterations in social function, communication, and repetitive behavior. Our efforts provide strong support for the hypothesis that altered 5-HT homeostasis can impact risk for ASD traits and provide a model with construct and face validity that can support further analysis of ASD mechanisms and potentially novel treatments.
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In the citing paper
“as well as altered basal firing of DR 5-HT neurons [120,121].”
From Neural circuits regulating prosocial behaviors (2023) · cites this paper as [120]
In the citing paper
“mice expressing a gain-of-function SERT variant that decreases 5-HT levels exhibit impaired sociability”
From Neural circuits regulating prosocial behaviors (2023) · cites this paper as [120]
In the citing paper
“SERT Ala56 mice exhibit whole-blood hyperserotonemia as well as brain and behavioral anomalies”
From Serotonin as a link between the gut-brain-microbiome axis in autism spectrum disorders (2018) · cites this paper as [55]
In the citing paper
“behavioral anomalies emulating those in ASD including repetitive behaviors, delayed communication and deficits in social interactions [55].”
From Serotonin as a link between the gut-brain-microbiome axis in autism spectrum disorders (2018) · cites this paper as [55]
In the citing paper
“including increased 5-HT clearance in the CNS, hypersensitivity of CNS 5-HT1A and 5-HT2A receptors”
From Serotonin as a link between the gut-brain-microbiome axis in autism spectrum disorders (2018) · cites this paper as [55]
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Citations
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Metadata
- Authors
- Veenstra-VanderWeele, J., Muller, C. L., Iwamoto, H., Sauer, J. E., Owens, W. A., Shah, C. R., Cohen, J., Mannangatti, P., Jessen, T., Thompson, B. J., Ye, R., Kerr, T. M., Carneiro, A. M., Crawley, J. N., Sanders-Bush, E., McMahon, D. G., Ramamoorthy, S., Daws, L. C., Sutcliffe, J. S., & Blakely, R. D.
- Affiliations
- Vanderbilt University (US)
- The University of Texas at San Antonio Health Science Center (US)
- National Institutes of Health (US)
- Departments of aPsychiatry,
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-03-19
- Volume
- 109
- Issue
- 14
- Pages
- 5469-5474
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3325657
- OpenAlex
- W2104220482
- Cited by
- 333
- References
- 76
- Citations by year
- 2026: 11 · 2025: 9 · 2024: 18 · 2023: 17 · 2022: 21 · 2021: 26 · 2020: 20 · 2019: 25 · 2018: 23 · 2017: 27 · 2016: 33 · 2015: 23 · 2014: 29 · 2013: 33 · 2012: 18
- FWCI
- 16.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Autism Speaks (AS2429)
- Vanderbilt University (HD15052)
- Vanderbilt Institute for Clinical and Translational Research (RR024975)
- H. Lundbeck A/S
- National Institutes of Health (HD-15052, RR024975)
- Vanderbilt Kennedy Center, Vanderbilt University Medical Center
- National Institute of Mental Health (R01MH094527, K08MH081066, MH081066, MH078098, R01MH062612, MH094604, MH-62612, R01MH094604, R03MH078098)
- National Institute on Drug Abuse (DA-07390, R01DA007390)
- National Center for Research Resources (RR024975, KL2RR024977, TL1RR024978, UL1RR024975)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD015052, HD 15052, HD065278, R01HD065278)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- autism spectrum disorder, hyperserotonemia, serotonin transporter, gain-of-function mutations, p38 MAPK, serotonin clearance, raphe neurons, 5-HT1A receptor, 5-HT2A receptor, receptor hypersensitivity, social dysfunction, repetitive behavior, transgenic mouse model
- MeSH terms
- Animals, Autistic Disorder, Disease Models, Animal, Homeostasis, Receptors, Serotonin, Serotonin, Social Behavior, Stereotyped Behavior, Mice
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