Cited2-KO Mouse

CITED2, also known as CBP/p300-interacting transactivator with Glu/Asp-rich C-terminal domain, 2, is a ubiquitously expressed transcription co-factor. It has a high affinity for the CH1 domain of CBP/p300, competing with hypoxia-inducible factors (HIFs). CITED2 is involved in numerous biological processes such as organ development, metabolic homeostasis, tissue regeneration, and immunity [1]. It can also influence fundamental cell processes like proliferation, apoptosis, differentiation, migration, and autophagy by interacting with various transcription factors and co-factors [2].

In mouse models, homozygous Cited2 gene deletion led to placental and fetal growth restriction, with disruptions in the junctional zone, delays in intrauterine trophoblast cell invasion, and compromised plasticity, indicating its importance in placental development [4]. Conditional deletion of Cited2 in adult mice markedly reduced the number of hematopoietic stem cells (HSCs) and compromised hematopoietic reconstitution, showing its role in hematopoiesis [3]. Myeloid-CITED2-deficient mice on the Apoe-/-background had larger atherosclerotic lesions, suggesting CITED2 restrains STAT1-IRF1 signaling in macrophages and limits atherogenesis [5]. Myeloid-CITED2 deficiency also exacerbated diet-induced obesity, insulin resistance, and adipose tissue inflammation, highlighting its role in restraining inflammation in macrophages [6]. In a cell model of myocardial ischemia/reperfusion injury, CITED2 was found to attenuate injury by inhibiting HIF-1α expression [7].

In conclusion, CITED2 is a crucial regulator in multiple biological processes. Studies using gene knockout (KO) and conditional knockout (CKO) mouse models have revealed its significance in placental development, hematopoiesis, and the prevention of diseases such as atherosclerosis, diet-induced obesity, and myocardial ischemia/reperfusion injury. These models have provided valuable insights into the functions of CITED2 and its potential as a therapeutic target.