Zfp384, also known as CIZ/NMP4 (Cas interacting zinc finger protein, Nuclear Matrix Protein 4), is a transcription factor. It is involved in regulating matrix-related proteins, and is associated with pathways related to bone metabolism, immune response, and cell cycle regulation [1,2,3]. Genetic models, such as knockout (KO) mice, are valuable for studying its functions.

In KO mouse models, CIZ/NMP4 deficiency suppresses the development of K/BxN-serum induced arthritis, reducing the invasion of inflammatory cells, bone resorption, and cartilage matrix degradation. This is likely through its regulation of key molecules like IL-1β, RANKL, and MMP-3 [1]. Nmp4-null mice have enhanced responses to intermittent parathyroid hormone (PTH) in terms of increasing trabecular bone mass and are immune to disuse-induced bone loss, suggesting it suppresses osteoblast function [2]. Conditional loss of Nmp4 in mesenchymal stem progenitor cells (MSPCs) enhances PTH-induced bone formation and Scl-mAb-induced increases in trabecular bone, while deletion in later osteoblast stages does not replicate these responses [4,5]. Nmp4-deficient mice are also protected from H1N1 influenza infection, with reduced recruitment of monocytes and neutrophils to the lungs and decreased expression of chemokine and pro-inflammatory cytokine genes [6].

In conclusion, Zfp384 plays crucial roles in bone metabolism, arthritis development, and the innate immune response. The study of Zfp384 KO and conditional knockout (CKO) mouse models has provided valuable insights into its functions in these disease-related biological processes, potentially guiding the development of new therapeutic strategies for osteoporosis, arthritis, and influenza-related lung inflammation.