| First Author | Xu J | Year | 2011 |
| Journal | Science | Volume | 334 |
| Issue | 6058 | Pages | 993-6 |
| PubMed ID | 21998251 | Mgi Jnum | J:177861 |
| Mgi Id | MGI:5296412 | Doi | 10.1126/science.1211053 |
| Citation | Xu J, et al. (2011) Correction of sickle cell disease in adult mice by interference with fetal hemoglobin silencing. Science 334(6058):993-6 |
| abstractText | Persistence of human fetal hemoglobin (HbF, alpha(2)gamma(2)) in adults lessens the severity of sickle cell disease (SCD) and the beta-thalassemias. Here, we show that the repressor BCL11A is required in vivo for silencing of gamma-globin expression in adult animals, yet dispensable for red cell production. BCL11A serves as a barrier to HbF reactivation by known HbF inducing agents. In a proof-of-principle test of BCL11A as a potential therapeutic target, we demonstrate that inactivation of BCL11A in SCD transgenic mice corrects the hematologic and pathologic defects associated with SCD through high-level pancellular HbF induction. Thus, interference with HbF silencing by manipulation of a single target protein is sufficient to reverse SCD. |
