Ctbp1-flox Mouse

Ctbp1, also known as C-terminal binding protein 1, is a transcriptional coregulator. It plays significant roles in various biological processes, such as neurodevelopment, hormone secretion, and membrane trafficking. It is involved in pathways related to gene transcription regulation, lipid and steroid hormone synthesis, and epithelial-mesenchymal transition (EMT) [1-6].

In neurodevelopment, de novo or maternally mosaic heterozygous mutations in Ctbp1, like c.991C > T (p.Arg342Trp) and c.1315_1316delCA (p.Gln439ValfsTer84), lead to phenotypes including intellectual disability, HADDTS syndrome, and cerebellar volume loss [1]. In polycystic ovary syndrome (PCOS) with metabolic syndrome, Ctbp1 in granulosa cells dysregulates steroid hormone and lipid synthesis by inhibiting aromatase gene transcription and promoting SREBP1a protein degradation [2]. In hepatocellular carcinoma, hypoxia-induced upregulation of Ctbp1 promotes EMT and sarcomatoid transformation, and knockdown of Ctbp1 can reverse this process [3]. In breast cancer cells, Ctbp1 transactivates RAD51, conferring cisplatin resistance [4]. In non-small-cell lung cancer, Ctbp1 promotes tumour-associated macrophage infiltration and cancer progression [5]. In keratinocytes, overexpression of Ctbp1 perturbs skin homeostasis, affecting epidermal proliferation, differentiation, and hair follicle morphogenesis [6].

In conclusion, Ctbp1 is a crucial transcriptional coregulator involved in multiple biological processes and disease conditions. Studies using genetic models, such as knockdown experiments in cell lines and animal models, have revealed its role in neurodevelopmental disorders, PCOS, cancer progression, and skin homeostasis. These findings enhance our understanding of the molecular mechanisms underlying these diseases and suggest Ctbp1 as a potential therapeutic target.