The roles of Mpdz and Kcnj9 in ethanal withdrawal: pleiotropic effects and potential mechanisms

This dissertation investigates the genetic contributions of Mpdz and Kcnj9 to ethanol withdrawal severity using mouse quantitative trait gene (QTG) models. Knockout studies demonstrate that both genes influence withdrawal-induced convulsions and may affect additional behaviors such as reduced locomotor activity, though effects on other ethanol‑related traits were less clear. A second focus examined mechanisms underlying Mpdz function. In vitro, reduced MPDZ expression increased 5HT2C receptor activity, and in vivo pharmacological studies supported a functional relationship between MPDZ and 5HT2C receptors. However, this interaction did not alter withdrawal severity. Overall, the findings strengthen evidence that Mpdz and Kcnj9 contribute to ethanol withdrawal phenotypes and highlight potential pathways for further investigation.