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rdf:type |
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lifeskim:mentions |
umls-concept:C0013935,
umls-concept:C0017262,
umls-concept:C0017645,
umls-concept:C0019054,
umls-concept:C0086418,
umls-concept:C0185117,
umls-concept:C0206745,
umls-concept:C0215398,
umls-concept:C0282641,
umls-concept:C0337112,
umls-concept:C0521457,
umls-concept:C1416657,
umls-concept:C1524075,
umls-concept:C2911684
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pubmed:issue |
5
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pubmed:dateCreated |
2000-3-29
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pubmed:abstractText |
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 beta-globin gene expression. To test whether beta-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 gamma-globin. Despite efficient production of hybrid malpha(2)-hgamma(2) 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 gamma-globin gene expression, may adversely affect other essential aspects of red blood cell physiology. (Blood. 2000;95:1827-1833)
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
95
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1827-33
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:10688844-Anemia,
pubmed-meshheading:10688844-Animals,
pubmed-meshheading:10688844-Crosses, Genetic,
pubmed-meshheading:10688844-DNA-Binding Proteins,
pubmed-meshheading:10688844-Fetal Death,
pubmed-meshheading:10688844-Genes, Lethal,
pubmed-meshheading:10688844-Genetic Complementation Test,
pubmed-meshheading:10688844-Globins,
pubmed-meshheading:10688844-Hemoglobins,
pubmed-meshheading:10688844-Hemolysis,
pubmed-meshheading:10688844-Humans,
pubmed-meshheading:10688844-Kruppel-Like Transcription Factors,
pubmed-meshheading:10688844-Mice,
pubmed-meshheading:10688844-Mice, Knockout,
pubmed-meshheading:10688844-Mice, Transgenic,
pubmed-meshheading:10688844-Protein Multimerization,
pubmed-meshheading:10688844-Species Specificity,
pubmed-meshheading:10688844-Transcription Factors,
pubmed-meshheading:10688844-Transgenes
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pubmed:year |
2000
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pubmed:articleTitle |
Fetal expression of a human Agamma globin transgene rescues globin chain imbalance but not hemolysis in EKLF null mouse embryos.
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pubmed:affiliation |
Children's Hospital and the Howard Hughes Medical Research Institute, and Harvard Medical School, Boston, MA 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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