Htr4, the 5-hydroxytryptamine receptor 4, is a serotonin receptor. Serotonin signaling through Htr4 is involved in various physiological processes. It participates in the regulation of gastrointestinal functions, such as influencing the secretion of hormones like glucagon-like peptide-1 (GLP-1) in the intestine [1]. It may also play a role in lung development and function, as well as in the regulation of growth traits in animals. Genetic models, like knockout (KO) mouse models, are valuable for studying its functions.

In Htr4-null mice, there is a 12% higher baseline lung resistance and increased methacholine-induced airway hyperresponsiveness, suggesting a causal relationship between Htr4 genetic variation and pulmonary function [2]. The Htr4 -/- phenotype in mouse is dependent on vagal innervation to the lung, indicating Htr4's role in pulmonary function may relate to neural innervation and control of breathing [3]. In rats, anhedonia may be associated with down-regulation of Htr4 expression in the hippocampus [4].

In conclusion, Htr4 is involved in multiple biological processes. Its role in pulmonary function, as revealed by KO mouse models, is related to neural innervation. Also, its dysregulation in the hippocampus may be associated with anhedonia-related conditions. These findings from model-based research contribute to understanding the biological functions of Htr4 and its implications in certain disease-related areas.

References:

1. Okumura, Motoshi, Hamada, Akihiro, Ohsaka, Fumina, Hira, Tohru, Sonoyama, Kei. 2020. Expression of serotonin receptor HTR4 in glucagon-like peptide-1-positive enteroendocrine cells of the murine intestine. In Pflugers Archiv : European journal of physiology, 472, 1521-1532. doi:10.1007/s00424-020-02453-7. https://pubmed.ncbi.nlm.nih.gov/32870377/

2. House, John S, Li, Huiling, DeGraff, Laura M, Zeldin, Darryl C, London, Stephanie J. 2014. Genetic variation in HTR4 and lung function: GWAS follow-up in mouse. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 29, 323-35. doi:10.1096/fj.14-253898. https://pubmed.ncbi.nlm.nih.gov/25342126/

3. House, John S, Nichols, Cody E, Li, Huiling, Zeldin, Darryl C, London, Stephanie J. 2017. Vagal innervation is required for pulmonary function phenotype in Htr4-/- mice. In American journal of physiology. Lung cellular and molecular physiology, 312, L520-L530. doi:10.1152/ajplung.00495.2016. https://pubmed.ncbi.nlm.nih.gov/28130264/

4. Bai, Mei, Zhu, Xiong-Zhao, Zhang, Yi, Zhong, Mingtian, Zhang, Xiuwu. 2014. Anhedonia was associated with the dysregulation of hippocampal HTR4 and microRNA Let-7a in rats. In Physiology & behavior, 129, 135-41. doi:10.1016/j.physbeh.2014.02.035. https://pubmed.ncbi.nlm.nih.gov/24582667/