ArticleMolecular autism2013
Genetic background modulates phenotypes of serotonin transporter Ala56 knock-in mice.
Article in Molecular autism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- Serotonergic Control of Gastrointestinal Development, Motility, and Inflammation.Comprehensive Physiology · 2023Article
- Rare Opportunities for Insights Into Serotonergic Contributions to Brain and Bowel Disorders: Studies of the SERT Ala56 Mouse.Frontiers in cellular neuroscience · 2021Article
- Familial Psychosis Associated With a Missense Mutation atFrontiers in genetics · 2021Article
- Turning strains into strengths for understanding psychiatric disorders.Molecular psychiatry · 2020Review
- Functional Interrogation of a Depression-Related Serotonergic Single Nucleotide Polymorphism, rs6295, Using a Humanized Mouse Model.ACS chemical neuroscience · 2019Article
- Extreme enhancement or depletion of serotonin transporter function and serotonin availability in autism spectrum disorder.Pharmacological research · 2019Review
- p38α MAPK signaling drives pharmacologically reversible brain and gastrointestinal phenotypes in the SERT Ala56 mouse.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- The Role of Bacteria, Probiotics and Diet in Irritable Bowel Syndrome.Foods (Basel, Switzerland) · 2018Review
- Analysis of neuroanatomical differences in mice with genetically modified serotonin transporters assessed by structural magnetic resonance imaging.Molecular autism · 2018Article
- Article
- Altered Cav1.2 function in the Timothy syndrome mouse model produces ascending serotonergic abnormalities.The European journal of neuroscience · 2017Article
- Mouse strain differences in SSRI sensitivity correlate with serotonin transporter binding and function.Scientific reports · 2017Article
- Serotonergic Mechanisms Regulating the GI Tract: Experimental Evidence and Therapeutic Relevance.Handbook of experimental pharmacology · 2017Review
- Serotonin neuron abnormalities in the BTBR mouse model of autism.Autism research : official journal of the International Society for Autism Research · 2017Article
- Article
- Serotonin transporter variant drives preventable gastrointestinal abnormalities in development and function.The Journal of clinical investigation · 2016Article
- The serotonin system in autism spectrum disorder: From biomarker to animal models.Neuroscience · 2016Review
- Reciprocal Effects on Neurocognitive and Metabolic Phenotypes in Mouse Models of 16p11.2 Deletion and Duplication Syndromes.PLoS genetics · 2016Article
- Translational Mouse Models of Autism: Advancing Toward Pharmacological Therapeutics.Current topics in behavioral neurosciences · 2016Review
- GABAB Receptor Agonist R-Baclofen Reverses Social Deficits and Reduces Repetitive Behavior in Two Mouse Models of Autism.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015Article
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundPreviously, we identified multiple, rare serotonin (5-HT) transporter (SERT) variants in children with autism spectrum disorder (ASD). Although in our study the SERT Ala56 variant was over-transmitted to ASD probands, it was also seen in some unaffected individuals, suggesting that associated ASD risk is influenced by the epistatic effects of other genetic variation. Subsequently, we established that mice expressing the SERT Ala56 variant on a 129S6/S4 genetic background display multiple biochemical, physiological and behavioral changes, including hyperserotonemia, altered 5-HT receptor sensitivity, and altered social, communication, and repetitive behavior. Here we explore the effects of genetic background on SERT Ala56 knock-in phenotypes.
methodsTo explore the effects of genetic background, we backcrossed SERT Ala56 mice on the 129 background into a C57BL/6 (B6) background to achieve congenic B6 SERT Ala56 mice, and assessed autism-relevant behavior, including sociability, ultrasonic vocalizations, and repetitive behavior in the home cage, as well as serotonergic phenotypes, including whole blood serotonin levels and serotonin receptor sensitivity.
resultsOne consistent phenotype between the two strains was performance in the tube test for dominance, where mutant mice displayed a greater tendency to withdraw from a social encounter in a narrow tube as compared to wildtype littermate controls. On the B6 background, mutant pup ultrasonic vocalizations were significantly increased, in contrast to decreased vocalizations seen previously on the 129 background. Several phenotypes seen on the 129 background were reduced or absent when the mutation was placed on the B6 background, including hyperserotonemia, 5-HT receptor hypersensivity, and repetitive behavior.
conclusionsOur findings provide a cogent example of how epistatic interactions can modulate the impact of functional genetic variation and suggest that some aspects of social behavior may be especially sensitive to changes in SERT function. Finally, these results provide a platform for the identification of genes that may modulate the risk of ASD in humans.
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