Htr3a, the main subunit of 5-hydroxytryptamine 3 (5-HT3) receptors, is a ligand-gated ion channel gene. 5-HT3 receptors are involved in multiple physiological processes. They are part of the serotonin pathway and play important roles in the central and peripheral nervous systems [2,4].

In knockout mouse models, Htr3a knockout (KO) mice showed autistic-like behaviors, impaired memory, and attenuated seizure susceptibility. Enhanced GABAergic transmission in pyramidal neurons and up-regulation of NMDAR were observed, suggesting NMDAR system could be a potential therapeutic target for autism related to HTR3A deficiency [1]. Conditional knockout of Setdb1 in neural progenitor cells led to up-regulation of Htr3a expression, increased number and excitability of Htr3a+ interneurons in the cortex, and Setdb1-Gad2-cKO mice showed anxiety-and depressive-like behaviors, which were partially reversed by a 5-HT3 receptor antagonist [3].

In conclusion, Htr3a is crucial for normal neural function as demonstrated by KO and conditional knockout mouse models. These models have revealed its role in conditions such as autism, anxiety, and depression, providing insights into potential therapeutic targets for these diseases.

References:

1. Huang, Lang, Wang, Jing, Liang, Guanmei, Zhong, Mei, Yang, Xinping. 2021. Upregulated NMDAR-mediated GABAergic transmission underlies autistic-like deficits in Htr3a knockout mice. In Theranostics, 11, 9296-9310. doi:10.7150/thno.60531. https://pubmed.ncbi.nlm.nih.gov/34646371/

2. Tone, Mitsuyo, Tahara, Shinichiro, Nojima, Satoshi, Okuzaki, Daisuke, Morii, Eiichi. 2020. HTR3A is correlated with unfavorable histology and promotes proliferation through ERK phosphorylation in lung adenocarcinoma. In Cancer science, 111, 3953-3961. doi:10.1111/cas.14592. https://pubmed.ncbi.nlm.nih.gov/32736413/

3. Li, Jiaqi, Zheng, Shenghui, Dong, Yuhao, Xiao, Lei, Jiang, Yan. 2022. Histone Methyltransferase SETDB1 Regulates the Development of Cortical Htr3a-Positive Interneurons and Mood Behaviors. In Biological psychiatry, 93, 279-290. doi:10.1016/j.biopsych.2022.08.021. https://pubmed.ncbi.nlm.nih.gov/36335068/

4. Niesler, Beate, Kapeller, Johannes, Hammer, Christian, Rappold, Gudrun. . Serotonin type 3 receptor genes: HTR3A, B, C, D, E. In Pharmacogenomics, 9, 501-4. doi:10.2217/14622416.9.5.501. https://pubmed.ncbi.nlm.nih.gov/18466097/