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Analysis of the human zeta-globin gene promoter in transgenic mice
DE Sabath, EA Spangler, EM Rubin and G Stamatoyannopoulos
Department of Medicine, University of Washington, Seattle 98195.
zeta-Globin is the embryonic form of the alpha chain of hemoglobin.
Transgenic mice generated with zeta-globin constructs containing the
zeta-globin gene, 557 bp of 5' flanking sequence, and 2-kb of 3' flanking
sequence linked to the beta-globin locus control region hypersensitive site
2 (HS2) expressed human zeta-globin only in embryonic yolk sac erythroid
tissue, and not in definitive erythroid tissue in the fetal liver or in
adult peripheral blood. To determine what sequences in the 5' flanking
region of the zeta-globin gene might be important for developmental
specificity, a series of 5' deletion constructs of the zeta-globin gene
were made and used to generate transgenic mice. The 5' ends of these
constructs were located 417, 207, and 128 bp 5' to the zeta-globin
transcriptional start site, and HS2 was included to increase the level of
erythroid-specific expression. In all lines of mice tested, human
zeta-globin was expressed only in embryonic tissue, and not in fetal livers
or in adult peripheral blood. Expression was independent of copy number and
appeared to be dependent on the site of transgene insertion. These data
suggest that the proximal 128 bp of the zeta-globin promoter is sufficient
to properly regulate zeta-globin expression during development.
Volume 82,
Issue 9,
pp. 2899-2905,
11/01/1993
Copyright © 1993 by The American Society of Hematology
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