What Gene Mutations Affect Serotonin in Mice?

Abstract

Although serotonin neurotransmission has been implicated in several neurodevelopmental and psychological disorders, the factors that drive dysfunction of the serotonin system are poorly understood. Current research regarding the serotonin system revolves around its dysfunction in neuropsychiatric disorders, but there is no database collating genetic mutations that result in serotonin abnormalities. To bridge this gap, we developed a list of genes in mice that, when perturbed, result in altered levels of serotonin either in brain or blood. Due to the intrinsic limitations of search, the current list should be considered a preliminary subset of all relevant cases. Nevertheless, it offered an opportunity to gain insight into what types of genes have the potential to impact serotonin by using gene ontology (GO). This analysis found that genes associated with monoamine metabolism were more often associated with increases in brain serotonin than decreases. Speculatively this could be because several pathways (and therefore many genes) are responsible for the clearance and metabolism of serotonin whereas only one pathway (and therefore fewer genes) is directly involved in the synthesis of serotonin. Another contributor could be cross talk between monoamine systems such as dopamine. In contrast, genes that were associated with decreases in brain serotonin were more likely linked to a developmental process. Sensitivity of serotonin neurons to developmental perturbations could due to their complicated neuroanatomy or possibly they may be negatively regulated by dysfunction of their innervation targets. Thus these observations suggest hypotheses regarding the mechanisms underlying the vulnerability of brain serotonin neurotransmission.

Understanding the molecular mechanisms of aggression in BALB/c and TPH2-deficient mice

“…besides Tph2−/−, which display altered 5-HT concentrations or metabolism (Tenpenny & Commons, 2017). For example, mice with a knockout for voltage-dependent N-type Ca(2+) channels display altered concentrations of brain 5-HT associated with excessive aggressive behaviors (Kim et al, 2009).…”