Humanized mouse models of Cooley's anemia: correct fetal-to-adult hemoglobin switching, disease onset, and disease pathology.
beta thalassemia major or Cooley's Anemia (CA) has been difficult to model in mice due to their lack of a fetal hemoglobin gene equivalent. This summary describes novel preclinical humanized mouse models of CA that survive on human fetal hemoglobin at birth and are blood-transfusion dependent for life upon completion of their human fetal-to-adult hemoglobin switch after birth. These CA models are the first to recapitulate the temporal onset of the disease in human patients. These novel humanized CA disease models are useful for the study of the regulation of globin gene expression, synthesis, and switching; examining the onset of disease pathology; development of transfusion and iron chelation therapies; induction of fetal hemoglobin synthesis; and the testing of novel genetic and cell-based therapies for the correction of thalassemia.
Huo
Yongliang
Y
Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
McConnell
Sean C
SC
Liu
Shanrun
S
Zhang
Tingting
T
Yang
Rui
R
Ren
Jinxiang
J
Ryan
Thomas M
TM
D017668:Age of Onset; D000818:Animals; D001803:Blood Transfusion; D004195:Disease Models, Animal; D005319:Fetal Hemoglobin / Q000235:genetics*; D015316:Genetic Therapy; D006454:Hemoglobins / Q000235:genetics*; D006801:Humans; D051379:Mice; D017086:beta-Thalassemia / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology* / Q000628:therapy
D006454:Hemoglobins; D005319:Fetal Hemoglobin