Cited1-flox Mouse

Cited1, also known as Cbp/P300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 1, is a transcriptional activator belonging to the non-DNA-binding transcription co-regulator family. It regulates diverse pathways such as the transforming growth factor/bone morphogenetic protein/SMAD, estrogen, Wnt-β-catenin, and androgen-AR signaling pathways by binding to CBP/p300 co-activators through its conserved transactivation domain CR2. Cited1 is important in embryonic development and has a regulatory role in the occurrence and development of various tumors [2].

Using a series of embryonic, adult-onset, and tissue/cell-specific loss-of-function mouse models, researchers found that hypothalamic Cited1 mediates estradiol-dependent leptin actions in pro-opiomelanocortin (Pomc) neurons, which control feeding. In arcuate Pomc neurons, Cited1 drives leptin's anorectic effects as a co-factor converging E2 and leptin signaling via direct Cited1-ERα-Stat3 interactions, contributing to the sexual dimorphism in diet-induced obesity [1]. In intestinal tumorigenesis, conditional deletion of Apc in the murine intestine upregulates Cited1. Crossing Cited1 null mice with Apc(Min/+) and AhCre(+)Apc(fl/fl) mice showed that Cited1 deficiency increases survival in Apc(Min/+) mice, impacts multiple oncogenic signaling pathways including Wnt, and suppresses intestinal tumorigenesis [3].

In conclusion, model-based research, especially using KO/CKO mouse models, has revealed that Cited1 plays a crucial role in energy homeostasis by mediating the interaction between estradiol and leptin in hypothalamic neurons. It also has an impact on tumorigenesis, such as in intestinal tumors. These findings contribute to our understanding of the biological functions of Cited1 in specific disease areas like diet-induced obesity and intestinal cancer.