RGD Reference Report - Correction of sickle cell disease in adult mice by interference with fetal hemoglobin silencing. - Rat Genome Database

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Correction of sickle cell disease in adult mice by interference with fetal hemoglobin silencing.

Authors: Xu, J  Peng, C  Sankaran, VG  Shao, Z  Esrick, EB  Chong, BG  Ippolito, GC  Fujiwara, Y  Ebert, BL  Tucker, PW  Orkin, SH 
Citation: Xu J, etal., Science. 2011 Nov 18;334(6058):993-6. doi: 10.1126/science.1211053. Epub 2011 Oct 13.
RGD ID: 11099996
Pubmed: PMID:21998251   (View Abstract at PubMed)
PMCID: PMC3746545   (View Article at PubMed Central)
DOI: DOI:10.1126/science.1211053   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
sickle cell anemia severityISOBcl11a (Mus musculus)11099996; 11099996 RGD 
sickle cell anemia severityIMP 11099996 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bcl11a  (BCL11 transcription factor A)

Genes (Mus musculus)
Bcl11a  (BCL11 transcription factor A)

Genes (Homo sapiens)
BCL11A  (BCL11 transcription factor A)


Additional Information