| First Author | Esteghamat F | Year | 2013 |
| Journal | Blood | Volume | 121 |
| Issue | 13 | Pages | 2553-62 |
| PubMed ID | 23361909 | Mgi Jnum | J:196405 |
| Mgi Id | MGI:5487884 | Doi | 10.1182/blood-2012-06-434530 |
| Citation | Esteghamat F, et al. (2013) Erythropoiesis and globin switching in compound Klf1::Bcl11a mutant mice. Blood 121(13):2553-62 |
| abstractText | B-cell lymphoma 11A (BCL11A) downregulation in human primary adult erythroid progenitors results in elevated expression of fetal gamma-globin. Recent reports showed that BCL11A expression is activated by KLF1, leading to gamma-globin repression. To study regulation of erythropoiesis and globin expression by KLF1 and BCL11A in an in vivo model, we used mice carrying a human beta-globin locus transgene with combinations of Klf1 knockout, Bcl11a floxed, and EpoR(Cre) knockin alleles. We found a higher percentage of reticulocytes in adult Klf1(wt/ko) mice and a mild compensated anemia in Bcl11a(cko/cko) mice. These phenotypes were more pronounced in compound Klf1(wt/ko)::Bcl11a(cko/cko) mice. Analysis of Klf1(wt/ko), Bcl11a(cko/cko), and Klf1(wt/ko)::Bcl11a(cko/cko) mutant embryos demonstrated increased expression of mouse embryonic globins during fetal development. Expression of human gamma-globin remained high in Bcl11a(cko/cko) embryos during fetal development, and this was further augmented in Klf1(wt/ko)::Bcl11a(cko/cko) embryos. After birth, expression of human gamma-globin and mouse embryonic globins decreased in Bcl11a(cko/cko) and Klf1(wt/ko)::Bcl11a(cko/cko) mice, but the levels remained much higher than those observed in control animals. Collectively, our data support an important role for the KLF1-BCL11A axis in erythroid maturation and developmental regulation of globin expression. |
