| First Author | Modepalli S | Year | 2022 |
| Journal | Exp Hematol | Volume | 114 |
| Pages | 22-32 | PubMed ID | 35973480 |
| Mgi Jnum | J:331429 | Mgi Id | MGI:7336580 |
| Doi | 10.1016/j.exphem.2022.08.001 | Citation | Modepalli S, et al. (2022) An In Vivo Model for Elucidating the Role of an Erythroid-Specific Isoform of Nuclear Export Protein Exportin 7 (Xpo7) in Murine Erythropoiesis. Exp Hematol |
| abstractText | Erythroid nuclear condensation is a complex process in which compaction to one-tenth its original size occurs in an active nucleus simultaneously undergoing transcription and cell division. We previously found that the nuclear exportin Exportin7 (Xpo7), which is erythroid- specific and highly induced during terminal erythropoiesis, facilitates nuclear condensation. We also identified a previously unannotated, erythroid-specific isoform of Xpo7 (Xpo7B) containing a novel first exon Xpo7-1b expressed only in late Ter119(+) erythroblasts. To better understand the functional difference between the erythroid Xpo7B isoform and the ubiquitous isoform (Xpo7A) containing the original first exon Xpo7-1a, we created gene-targeted mouse models lacking either exon Xpo7-1a or Xpo7-1b, or both exons 4 and 5, which are completely null for Xpo7 expression. We found that deficiency in Xpo7A does not affect steady-state nor stress erythropoiesis. In contrast, mice lacking the erythroid isoform, Xpo7B, exhibit a mild anemia as well as altered stress erythropoiesis. Complete Xpo7 deficiency resulted in partially penetrant embryonic lethality at the stage when definitive erythropoiesis is prominent in the fetal liver. Inducible complete knockdown of Xpo7 confirms that both steady-state erythropoiesis and stress erythropoiesis are affected. We also observe that Xpo7 deficiency downregulates the expression of important stress response factors, such as Gdf15 and Smad3. We conclude that the erythroid-specific isoform of Xpo7 is important for both steady-state and stress erythropoiesis in mice. |
