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Blood, Vol. 92 No. 9 (November 1), 1998:
pp. 3057-3063
RAPID COMMUNICATION
Reversal of Lethal  - and  -Thalassemias in Mice by Expression of
Human Embryonic Globins
J. Eric Russell and
Stephen A. Liebhaber
From the Departments of Medicine (Hematology/Oncology), Pediatrics
(Hematology), and Genetics, and the Howard Hughes Medical Institute,
University of Pennsylvania School of Medicine, Philadelphia.
Genetic mutations that block  - or  -globin gene expression in
humans can result in severe and frequently lethal thalassemic phenotypes. Homozygous inactivation of the endogenous - or
-globin genes in mice results in corresponding thalassemic syndromes
that are uniformly fatal in utero. In the current study, we show that the viability of these mice can be rescued by expression of human embryonic  - and  -globins, respectively. The capacity of embryonic globins to fully substitute for their adult globin homologues is
further demonstrated by showing that - and -globins reverse the
hemolytic anemia and abnormal erythrocyte morphology of mice with
nonlethal forms of - and -thalassemia. These results illustrate the potential therapeutic utility of embryonic globins as substitutes for deficient adult globins in thalassemic individuals. Moreover, the
capacity of embryonic globins to functionally replace their adult
homologues brings into question the physiologic basis for globin gene
switching.
© 1998 by The American Society of Hematology.
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