GNAT3, also known as gustducin, is the α subunit of a G-protein that governs sweet, savory, and bitter taste transduction pathways [3]. It plays a crucial role in taste-related chemosensory signaling and is involved in maintaining tissue homeostasis in non-gustatory tissues [2]. Genetic models, such as gene-knockout (KO) mouse models, are valuable for studying GNAT3's functions.

In pancreatic cancer, Gnat3-null (Gnat3-/-) mice crossed with mice driving oncogenic KRAS expression in the pancreas (KC mice) showed that ablation of Gnat3 in KC organoids increased the release of tumor-promoting cytokines like CXCL1 and CXCL2. Aged Gnat3-/-;KC mice progressed more rapidly to metastatic carcinoma compared with KC controls, suggesting that GNAT3 suppresses pancreatic cancer progression by modulating the CXCL1/2-CXCR2 axis and the myeloid-derived suppressor cell (MDSC) population [1].

In periodontitis, Ga-gustducin-null (Gnat3-/-) mice were used to validate that salicin, which activates Tas2r143-mediated bitter taste signaling via GNAT3 in gingival fibroblasts, alleviates periodontitis. The anti-inflammatory effects of salicin were abolished in Gnat3-/-mice, indicating that GNAT3 in gingival fibroblasts is critical for maintaining periodontal homeostasis [2].

In conclusion, GNAT3 is essential for taste-related chemosensory signaling and tissue homeostasis. Studies using Gnat3 KO mouse models have revealed its significance in pancreatic cancer progression and periodontitis. These findings provide insights into the biological functions of GNAT3 and potential therapeutic targets for related diseases.