Hic2, also known as HIC ZBTB transcriptional repressor 2, is a gene involved in multiple biological processes. It plays a crucial role in cardiac development and is associated with the regulation of hemoglobin switching. Genetic models, such as mouse models, are valuable for studying its functions [3,4,5].

In cardiac development, a genetrap mouse allele of Hic2 showed that homozygosity for the allele was embryonic lethal before E10.5, while heterozygous embryos had a partially penetrant late lethality and one-third of them had a cardiac phenotype like ventricular septal defect with over-riding aorta. Conditional targeting indicated its requirement within the Nkx2.5+ and Mesp1+ cardiovascular progenitor lineages [5].

In hemoglobin switching, Hic2 represses BCL11A transcription. Forced expression of Hic2 in adult erythroid cells inhibits BCL11A transcription and induces fetal β-type globin (HBG) expression, while loss of Hic2 in fetal erythroblasts increases BCL11A transcription. Let-7 miRNAs repress Hic2, regulating BCL11A transcription and hemoglobin switching [1,2].

In glioma, Hic2 is hypermethylated and expressed at low levels, predicting poor prognosis. Overexpression of Hic2 inhibits glioma cell proliferation in vitro and in vivo [3].

In conclusion, Hic2 is an important regulator in cardiac development and hemoglobin switching. Mouse models, especially KO/CKO models, have been instrumental in revealing its functions in these processes. In addition, its role in glioma prognosis and growth regulation provides potential implications for glioma treatment.