C57BL/6JCya-Tle3^em1/Cya

Tle3, also known as Transducin-like enhancer of split 3, is a transcriptional cofactor or corepressor. It is involved in multiple signaling pathways and plays a crucial role in maintaining lineage fidelity in various cell types, and is associated with processes like cell differentiation, immune regulation, and cancer development. Genetic models, such as KO or CKO mouse models, have been essential for studying its functions.

In antigen-responding CD8+ T cells, genetic ablation of Tle3 promoted CD8+ TCM cell formation at the expense of CD8+ TEM cells, indicating its role in controlling effector and central memory CD8+ T cell fates [1]. In luminal breast cancer, TLE3 actively repressed the gene-expression signature associated with basal-like breast cancers, preventing a hybrid epithelial-mesenchymal state and reducing metastatic capacity [2]. Myeloid-specific knockout of Tle3 in mice led to increased numbers of regulatory T and TH17 cells in the colonic lamina propria, disrupting intestinal immune homeostasis [3]. Loss of TLE3 in LNCaP prostate cancer cells conferred resistance to AR antagonists [4]. In C2C12 myogenic cells, Tle3 depletion led to reduced expression of myogenic differentiation genes and impaired differentiation [5]. In colorectal cancer, TLE3 was down-regulated, and its overexpression repressed cancer cell proliferation by inhibiting MAPK and AKT signaling pathways [6]. Conditional deletion of TLE3 in adipocytes promoted mitochondrial oxidative metabolism and improved glucose control [7].

In conclusion, Tle3 is a key regulator in multiple biological processes. Model-based research, especially KO/CKO mouse models, has revealed its significance in diseases such as breast cancer, prostate cancer, colorectal cancer, and in immune-related disorders. These findings provide insights into potential therapeutic strategies targeting Tle3 for treating associated diseases.