Strict in vivo specificity of the Bcl11a erythroid enhancer

Autor:	Daniel E. Bauer, Donyell M. Croney, Yuko Fujiwara, Luciano C. Greig, Jeffrey D. Macklis, Matthew Nguyen, Mollie B. Woodworth, Elenoe C. Smith, Sidinh Luc, Falak Sher, Stuart H. Orkin
Rok vydání:	2016
Předmět:	0301 basic medicine Phenocopy business.industry Immunology Repressor Hematopoietic stem cell Cell Biology Hematology Biochemistry Cell biology 03 medical and health sciences 030104 developmental biology medicine.anatomical_structure In vivo Regulatory sequence Medicine Globin business Enhancer Gene
Zdroj:	Blood. 128:2338-2342
ISSN:	1528-0020 0006-4971
DOI:	10.1182/blood-2016-08-736249
Popis:	BCL11A, a repressor of human fetal (γ-)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 (Δenh), 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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::a3dc629cd1765a3f625cf2551f05a3d9 https://doi.org/10.1182/blood-2016-08-736249 Zobrazit plný text záznamu