Xpo7, also known as exportin 7, is a bidirectional transporter that regulates the nuclear-cytoplasmic shuttling of a wide range of substrates [4]. It is involved in multiple biological pathways. For example, it negatively regulates Hedgehog signaling by exporting Gli2 from the nucleus [3], and is also associated with pathways like cell cycle-related and PI3K-AKT pathways [2]. It has significance in processes such as senescence, erythropoiesis, and is linked to diseases including cancer and schizophrenia [1,5,6]. Genetic models, especially KO/CKO mouse models, are valuable for studying its functions.

In gene-targeted mouse models, deficiency in the erythroid-specific isoform Xpo7B leads to a mild anemia and altered stress erythropoiesis, while deficiency in Xpo7A has no impact on steady-state or stress erythropoiesis. Complete Xpo7 deficiency results in partially penetrant embryonic lethality during definitive erythropoiesis in the fetal liver, and inducible complete knockdown affects both steady-state and stress erythropoiesis. Xpo7 deficiency also downregulates important stress response factors [6]. In a liver cancer mouse model, depletion of Xpo7 alleviated oncogene-induced senescence (OIS) and increased tumor formation, suggesting it is a tumor suppressor regulating p21CIP1-dependent senescence [1].

In conclusion, Xpo7 is crucial for erythropoiesis, with its erythroid-specific isoform playing a key role in both steady-state and stress conditions. In cancer, it functions as a tumor suppressor through regulating senescence-related mechanisms. The study of Xpo7 using KO/CKO mouse models has provided valuable insights into its functions in erythropoiesis and cancer, enhancing our understanding of these biological processes and disease conditions.