Hdc-KO Mouse

Hdc, or histidine decarboxylase, is a rate-limiting enzyme for histamine synthesis. Histamine is a critical mediator of anaphylaxis, a neurotransmitter, and a regulator of gastric acid secretion. Hdc is expressed both in the posterior hypothalamus and peripherally, and its encoded enzyme is essential for histamine biosynthesis, which is involved in various biological processes such as immune regulation and neurotransmission [3,4]. Gene knockout mouse models have been valuable in studying Hdc's function.

In Hdc -/- mice, neutrophils are disorderly recruited into the ischemic injured area of the myocardium. Hdc deficiency leads to attenuated adhesion but enhanced migration and augmented ROS/NETs production in neutrophils, with Hdc -/- mouse-derived NETs promoting cardiomyocyte death and cardiac fibroblast proliferation/migration. Also, protein arginine methyltransferase 1 (PRMT1) is increased in Hdc -/- mouse-derived neutrophils [1].

In another study, Hdc-expressing myeloid-derived suppressor cells were found to promote basal-like transition and metastasis of breast cancer, and targeted ablation of Hdc+ PMN-MDSCs-derived Wnts hampered the metastatic cascade [2]. Chronic stress downregulates Hdc expression in ovarian cancer tumors, accelerating cancer growth, while exogenous histamine treatment alleviates this effect [5].

In Hdc knockout mice, genes associated with oligodendrocytes and myelin production are upregulated in the dorsal striatum, and there is reduced fractional anisotropy in the dorsal striatum, which may be related to the pathophysiology of Tourette syndrome [6]. Histamine deficiency in Hdc knockout mice exacerbates cisplatin-induced ferroptosis in cochlea hair cells [7].

In conclusion, Hdc is crucial for histamine synthesis and plays significant roles in multiple biological processes and disease conditions. The use of Hdc knockout mouse models has revealed its functions in cardiovascular diseases, breast cancer, ovarian cancer, Tourette syndrome-related pathophysiology, and cisplatin-induced ototoxicity, providing insights into disease mechanisms and potential therapeutic targets.