Hdc, or histidine decarboxylase, is a crucial enzyme for histamine synthesis [3,4,5,6,7]. Histamine is involved in various physiological functions, acting as a mediator in anaphylaxis, a neurotransmitter, and a regulator of gastric acid secretion [3]. The Hdc gene has significance in multiple biological pathways, with its expression influencing processes related to the immune system, neural function, and cell metabolism [1,2,4]. Gene knockout mouse models, such as Hdc -/- mice, have been valuable for studying Hdc's function in vivo [1,2,4,5,6,7].

In Hdc -/- mice, neutrophils show disorderly recruitment to the ischemic injured myocardium, along with enhanced migration, increased ROS/NETs production, which promotes cardiomyocyte death and cardiac fibroblast proliferation/migration. This is associated with increased PRMT1 expression in neutrophils, and histamine treatment can reverse these effects, unveiling the HDC role in NETosis through the histamine-H1R-ATP-SWI/SNF-PRMT1-ROS signaling pathway [1]. Hdc -expressing myeloid-derived suppressor cells promote basal-like transition and metastasis of breast cancer by activating Wnt/β-catenin signaling in CK14+ malignant cells [2]. In Hdc knockout mice, genes related to oligodendrocytes and myelin production are upregulated in the dorsal striatum, suggesting abnormal myelination, consistent with findings in patients with tics [6]. Also, histamine deficiency in HDC knockout mice exacerbates cisplatin-induced ferroptosis in cochlea hair cells [7].

In summary, Hdc is essential for histamine synthesis and is involved in numerous biological processes. Studies using Hdc knockout mouse models have revealed its significant roles in cardiovascular diseases, breast cancer metastasis, neurodevelopmental disorders like Tourette syndrome, and ototoxicity. These findings enhance our understanding of disease mechanisms and may provide new therapeutic targets.