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

The study was done in mice, not in people, so it does not show how serotonin transporter changes affect human brain structure or clinical outcomes. The MRI analysis used 56-μm isotropic voxels, so differences at cellular or microscopic scale would be missed, including known whisker barrel cortex organization changes in knockout mice. Mice were scanned only at 60 ± 2 days of age, so early developmental differences could have been missed. Behavior was not tested in the mice that were imaged, so the paper cannot link the observed volume differences to the behavioral phenotypes reported for these models. For the knockout group, C57BL/6 wild-type mice from Jackson Laboratory were used as controls instead of wild-type littermates, because the purchased knockout line did not provide littermate controls. The knockout and knockin mice came from different colonies, so cross-model comparisons required statistical normalization of wild-type controls. Maternal genotype was held constant by using heterozygous crosses for the knockin group, so possible maternal serotonin effects were not examined.

Funding: National Institutes of Health, Ontario Brain Institute, Canadian Institute for Health Research, and Ontario Mental Health Foundation. The supplied text does not report author conflicts of interest.

Do not read these mouse brain volume differences as evidence that serotonin transporter variants cause autism in patients or that changing serotonin transport would alter human brain structure. The study measured adult mouse brains, not human patients, and the gain-of-function variant alone did not produce significant volume differences.