Although the murine Htr3a gene was the focus of the present studies, many additional studies indicate important differences between naturally occurring human Htr3a and Htr3b variants. For example, five naturally occurring human Htr3a variants cause changes in the cell surface expression of 5-HT3 receptors [62]. More recently four naturally occurring variants of the human Htr3b gene were found to alter the expression and function of heteromeric 5-HT3A/B receptors [63]. Many gene association studies linking variants of these genes with depression, bipolar affective disorder, nausea, and other phenotypes are available. One functional variant of the Htr3b gene has particularly strong linkage to depression in women and nausea after antidepressant administration [64,65].
