| First Author | Smith EC | Year | 2016 |
| Journal | Blood | Volume | 128 |
| Issue | 19 | Pages | 2338-2342 |
| PubMed ID | 27707736 | Mgi Jnum | J:239331 |
| Mgi Id | MGI:5828338 | Doi | 10.1182/blood-2016-08-736249 |
| Citation | Smith EC, et al. (2016) Strict in vivo specificity of the Bcl11a erythroid enhancer. Blood 128(19):2338-2342 |
| abstractText | BCL11A, a repressor of human fetal (gamma-)globin expression, is required for immune and hematopoietic stem cell functions and brain development. Regulatory sequences within the gene, which are subject to genetic variation affecting fetal globin expression, display hallmarks of an erythroid enhancer in cell lines and transgenic mice. As such this enhancer is a novel, attractive target for therapeutic gene editing. To explore the roles of such sequences in vivo, we generated mice in which the orthologous 10 kb intronic sequences were removed. Bcl11a-enhancer deleted mice (Bcl11a(Deltaenh)) phenocopy the BCL11A-null state with respect to alterations of globin expression, yet are viable and exhibit no observable blood, brain, or other abnormalities. These preclinical findings provide strong in vivo support for genetic modification of the enhancer for therapy of hemoglobin disorders. |
