Hrh2, the gene encoding the histamine H2 receptor, is closely associated with multiple biological processes and diseases. Histamine, via binding to HRH2, is involved in various pathways such as the regulation of gastric acid secretion, and also plays roles in the cardiovascular, nervous, and immune systems [2,3,4]. Genetic models like knockout mice are valuable tools for studying its functions.

To understand the role of endothelial HRH2, endothelial-specific Hrh2 knockout (ECKO) mice were generated. Hrh2ECKO mice were normal, healthy, and fertile, yet these models can potentially be used to explore HRH2's role in the development and treatment of related diseases [1]. In the context of schizophrenia, selective knockout of Hrh2 in glutamatergic neurons induced schizophrenia-like phenotypes, suggesting that Hrh2 deficit in these neurons may be pivotal to the pathogenesis of schizophrenia [4].

In conclusion, Hrh2, through its encoded receptor HRH2, is involved in diverse biological functions. The generation of Hrh2 knockout mouse models, especially the endothelial-specific and glutamatergic neuron-specific ones, has provided insights into its role in diseases such as those related to the endothelium and schizophrenia. These models contribute to a better understanding of disease mechanisms and potential therapeutic strategies.