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Molecular Autism
Published in: Molecular Autism 1/2018

Open Access 01-12-2018 | Research

Analysis of neuroanatomical differences in mice with genetically modified serotonin transporters assessed by structural magnetic resonance imaging

Authors: Jacob Ellegood, Yohan Yee, Travis M. Kerr, Christopher L. Muller, Randy D. Blakely, R. Mark Henkelman, Jeremy Veenstra-VanderWeele, Jason P. Lerch

Published in: Molecular Autism | Issue 1/2018

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Abstract

Background

The serotonin (5-HT) system has long been implicated in autism spectrum disorder (ASD) as indicated by elevated whole blood and platelet 5-HT, altered platelet and brain receptor and transporter binding, and genetic linkage and association findings. Based upon work in genetically modified mice, 5-HT is known to influence several aspects of brain development, but systematic neuroimaging studies have not previously been reported. In particular, the 5-HT transporter (serotonin transporter, SERT; 5-HTT) gene, Slc6a4, has been extensively studied.

Methods

Using a 7-T MRI and deformation-based morphometry, we assessed neuroanatomical differences in an Slc6a4 knockout mouse on a C57BL/6 genetic background, along with an Slc6a4 Ala56 knockin mouse on two different genetic backgrounds (129S and C57BL/6).

Results

Individually (same sex, same background, same genotype), the only differences found were in the female Slc6a4 knockout mouse; all the others had no significant differences. However, an analysis of variance across the whole study sample revealed a significant effect of Slc6a4 on the amygdala, thalamus, dorsal raphe nucleus, and lateral and frontal cortices.

Conclusions

This work shows that an increase or decrease in SERT function has a significant effect on the neuroanatomy in 5-HT relevant regions, particularly the raphe nuclei. Notably, the Slc6a4 Ala56 knockin alone appears to have an insignificant, but suggestive, effect compared to the KO, which is consistent with Slc6a4 function. Despite the small number of 5-HT neurons and their localization to the brainstem, it is clear that 5-HT plays an important role in neuroanatomical organization.
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Metadata
Title
Analysis of neuroanatomical differences in mice with genetically modified serotonin transporters assessed by structural magnetic resonance imaging
Authors
Jacob Ellegood
Yohan Yee
Travis M. Kerr
Christopher L. Muller
Randy D. Blakely
R. Mark Henkelman
Jeremy Veenstra-VanderWeele
Jason P. Lerch
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Molecular Autism / Issue 1/2018
Electronic ISSN: 2040-2392
DOI
https://doi.org/10.1186/s13229-018-0210-z

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