CITED2, also known as CBP/p300-interacting transactivator with Glu/Asp-rich C-terminal domain 2, is a ubiquitously expressed protein. It has a high affinity for the CH1 domain of transcriptional co-activators CBP/p300, competing with hypoxia-inducible factors (HIFs). CITED2 is involved in diverse physiological processes, such as organ development, metabolic homeostasis, tissue regeneration, and immunity. It also plays roles in multiple disease conditions, including kidney and heart diseases, type 2-diabetes, and cancer [1].

In placental development, homozygous Cited2 gene deletion in rats led to placental and fetal growth restriction, with disruptions in the junctional zone and delays in trophoblast cell invasion [3]. In hematopoiesis, fetal liver cells from Cited2 null embryos had reduced hematopoietic colonies and impaired reconstitution capacity, and conditional deletion of Cited2 in adult mice decreased the number of hematopoietic stem cells (HSCs) [2]. In atherosclerotic disease, myeloid-CITED2-deficient mice on the Apoe-/-background had larger atherosclerotic lesions [4]. In diet-induced obesity, myeloid-CITED2 deficiency exacerbated obesity, glucose intolerance, and adipose tissue inflammation [5].

In conclusion, CITED2 is a key regulator in various biological processes. Gene knockout (KO) and conditional knockout (CKO) mouse models have revealed its importance in placental development, hematopoiesis, and in diseases like atherosclerosis and diet-induced obesity. These models contribute to understanding the role of CITED2 in specific disease areas, providing insights into potential therapeutic strategies.