Gper1, also known as GPR30, is a G protein-coupled estrogen receptor. It binds 17-β-estradiol with high affinity and is involved in non-genomic signaling by estrogens, activating kinase cascades and calcium flux within cells [2]. It plays a role in multiple biological processes and is associated with various physiological functions and disease conditions, making genetic models like KO mouse models valuable for its study.

In a KO mouse model study, GPER1-KO males showed reduced anxiety in the elevated plus maze, while GPER1-KO females had a specifically increased fear response in a contextual fear conditioning paradigm. In the Morris water maze, spatial learning and memory consolidation were impaired in both sexes due to GPER1 deficiency. In addition, GPER1-KO led to changes in synaptic excitability and protein expression in the hippocampus, indicating sex-specific modulatory functions of GPER1 in the hippocampal network [3]. In another study, Gper1 deletion in male UUO mice accelerated renal fibrosis and increased inflammation, suggesting its role in macrophage-mediated renal fibrosis [1].

In conclusion, Gper1 plays crucial roles in multiple biological processes. Model-based research, especially KO mouse models, has revealed its sex-specific functions in the hippocampal network related to cognitive function and mood, as well as its role in macrophage-mediated renal fibrosis. These findings contribute to understanding the mechanisms of related diseases and may provide potential therapeutic targets.