Gse1-flox Mouse

GSE1, also known as Gse1 coiled-coil protein or KIAA0182, is a proline-rich protein. It is a component of the CoREST complex which acts as an H3K4 and H3K9 demethylase and regulates gene expression. GSE1 is involved in the DNA damage response (DDR) pathway as it forms a complex with the HDAC1/CoREST deacetylase/demethylase co-repressor complex, and is essential for the binding of the deubiquitinase USP22 to CoREST during DDR [1].

Gse1 knockout (KO) mouse models have shown that Gse1 is required for placenta development. Maternal deletion of Gse1 leads to a high incidence of prenatal death, and zygotic deletion results in embryonic lethality from E12.5 and perinatal death. The Gse1 mutant placenta exhibits histological defects from E14.5, deficient in MCT4+ syncytiotrophoblast II [2].

In cancer-related functional studies, GSE1 depletion in various cancer cell lines has demonstrated its oncogenic role. For example, in lung adenocarcinoma cells, GSE1 depletion inhibits proliferation and migration by downregulating KLF6 expression [3]. In gastric cancer cells, overexpression of GSE1 is related to trastuzumab resistance, and its depletion decreases this resistance [4]. In breast cancer, silencing of GSE1 significantly suppresses cell proliferation, migration and invasion [5]. In castration-resistant prostate cancer, GSE1 promotes oncogenic and recurrent phenotypes by targeting TACSTD2 [6].

In conclusion, GSE1 is a key component of the CoREST complex with important functions in gene regulation and the DNA damage response. Studies using KO mouse models have revealed its crucial role in placenta development. In the context of cancer, GSE1 shows oncogenic properties across multiple cancer types, suggesting that it could be a potential therapeutic target for these diseases.