Htr3a, encoding the 5-hydroxytryptamine receptor 3A, is a key subunit of the 5-HT3 ligand-gated ion channels. These channels are involved in multiple biological processes, and the 5-HT3 receptors play roles in chemotherapy-induced nausea and vomiting, irritable bowel syndrome, and psychiatric disorders [2].

In gene knockout studies, Htr3a knockout (KO) mice showed autistic-like behaviors, impaired memory, and attenuated seizure susceptibility. Enhanced GABAergic transmission and a decreased excitatory/inhibitory ratio were observed in pyramidal neurons, with upregulation of NMDAR in PV + interneurons, suggesting a role in autism-related pathogenesis [1]. Also, Setdb1-Gad2-cKO mice, with implications for Htr3a regulation, exhibited anxiety-and depressive-like behaviors, which were partially reversed by a 5-HT3 receptor antagonist, indicating Htr3a's role in mood regulation [3]. In addition, Htr3a deletion promoted SSRI efficacy and blocked stress-induced gene modification in the cortex, suggesting its potential as a target for stress-related disorders [4].

In conclusion, Htr3a is crucial in the context of neurological and psychiatric conditions. Studies using KO and CKO mouse models have revealed its role in behaviors related to autism, mood, and stress-related disorders, providing insights into potential therapeutic targets for these diseases.