Fetal expression of a human Aγ globin transgene rescues globin chain imbalance but not hemolysis in EKLF null mouse embryos

A. C. Perkins, K. R. Peterson, G. Stamatoyannopoulos, H. E. Witkowska, Stuart H. Orkin

Research output: Contribution to journalArticleResearchpeer-review

43 Citations (Scopus)

Abstract

Mice lacking the erythroid Kruppel-like factor (EKLF) die in utero at embryonic day 15 (E15) from severe anemia. EKLF-/embryos display a marked deficit in β-globin gene expression. To test whether β-globin deficiency was solely responsible for the anemia and intrauterine death, we corrected the globin chain imbalance in EKLF(-/-) embryos by breeding with a strain of mice that express high levels of human γ-globin. Despite efficient production of hybrid mα2-hγ2 hemoglobin in the fetal livers of EKLF(-/-) animals, hemolysis was not corrected and survival was not prolonged. We concluded that deficiency of nonglobin EKLF target genes is a major contributor to the definitive red blood cell abnormalities and prenatal death in EKLF(-/-) embryos. These results suggest that strategies designed to antagonize EKLF function in adults with hemoglobinopathy. In an attempt to reactivate γ-globin gene expression, may adversely affect other essential aspects of red blood cell physiology. (C) 2000 by The American Society of Hematology.

Original languageEnglish
Pages (from-to)1827-1833
Number of pages7
JournalBlood
Volume95
Issue number5
Publication statusPublished - 1 Mar 2000
Externally publishedYes

Cite this