Zc3h12a, also known as MCPIP1 and Regnase-1, is the founding member of a ribonuclease family. It is an extensively studied regulator of the inflammatory response, acting as an RNase to degrade chemokine transcripts like IL-1 and its own mRNA, and as a transcription factor to reduce the expression of other chemokines induced by NF-kβ such as MCP-1. It also up-regulates genes involved in differentiation and apoptosis, playing a crucial role in maintaining an equilibrium in the immune response [1,2].

In the KC-Tie2 inflammatory dermatitis mouse model, siRNA knockdown of TCF4 led to increased Zc3h12a expression, creating a self-sustaining inflammatory feedback cycle. Zc3h12a knockdown decreased the expression of pro-inflammatory genes, revealing its pro-inflammatory role in skin inflammation [3]. In small cell lung cancer cells, knockdown of Zc3h12a impaired DNA repair ability, as seen by decreased BRCA1 expression and increased γH2AX at DNA damage sites, and sensitized the cells to radiotherapy [4]. Macrophage-specific Mcpip1 (Zc3h12a) deficiency in mice led to a more severe DSS-induced colitis, with increased macrophage migratory capacity and M1 polarisation but decreased monocyte-to-macrophage maturation, highlighting its role in mucosal inflammation [5].

In conclusion, Zc3h12a plays essential roles in inflammation-related biological processes, as revealed through model-based research. Its functions in maintaining immune equilibrium, regulating skin and mucosal inflammation, and affecting DNA damage repair in small cell lung cancer are significant. Mouse models, including KO/CKO models, have been crucial in uncovering these roles, providing insights into diseases such as inflammatory skin diseases, small cell lung cancer, and inflammatory bowel disease.