Zdhhc18-flox Mouse

Zdhhc18, encoding a palmitoyltransferase, is involved in palmitoylation, an important post-translational modification. Palmitoylation participates in regulating diverse biological processes, and Zdhhc18-mediated palmitoylation is associated with innate immunity, metabolism, and fibrosis-related pathways, which are crucial for maintaining normal physiological functions and are related to disease development [1,2,3].

In innate immunity, Zdhhc18-deficient mice were resistant to DNA virus infection. Zdhhc18 negatively regulated cGAS-mediated innate immune responses by catalyzing cGAS palmitoylation at C474, which restricted cGAS enzymatic activity and inhibited its dimerization [1].

In ovarian cancer, MDH2 palmitoylation by Zdhhc18 activated mitochondrial respiration and promoted cancer cell growth. Silencing MDH2 repressed mitochondrial respiration and cell proliferation both in vitro and in vivo [2].

In renal fibrosis, tubule-specific deletion of ZDHHC18 attenuated tubular epithelial cells' partial epithelial-mesenchymal transition, reducing profibrotic cytokine production and alleviating tubulointerstitial fibrosis [3].

In conclusion, Zdhhc18 plays significant roles in innate immunity, cancer metabolism, and renal fibrosis through its palmitoyltransferase function. Studies using Zdhhc18-deficient mouse models have revealed its regulatory effects on cGAS-mediated innate immunity, ovarian cancer growth, and renal fibrosis development, providing potential therapeutic targets for related diseases.