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Changes in alpha-globin gene expression in mice of two alpha-globin haplotypes during development
1Biology Division, Oak Ridge National Laboratory, Tennessee.
Biochemical Genetics
|October 1, 1990
Summary
Mouse alpha-globin ratios shift during embryonic development in nucleated red cells but not in nonnucleated cells. These changes reflect altered globin gene transcription and affinities during hemoglobin formation.
Area of Science:
- Developmental biology
- Hematopoiesis
- Molecular genetics
Background:
- Adult alpha-globin is crucial for mouse development, synthesized initially in primitive nucleated erythrocytes and later in definitive nonnucleated erythrocytes.
- Hemoglobin composition changes throughout gestation, involving different alpha-globin chains.
Purpose of the Study:
- To investigate the developmental changes in alpha-globin ratios in mouse erythrocytes.
- To compare alpha-globin ratios between different haplotypes (Hbag2 and Hbac) during gestation.
- To understand the molecular mechanisms underlying alpha-globin ratio regulation.
Main Methods:
- Isoelectric focusing analysis of hemoglobins from mice with Hbag2 and Hbac haplotypes.
- Analysis of red blood cells at different gestational ages (day 11.5 to day 16.5).
Main Results:
- Alpha-globin ratios changed between gestational days 11.5 and 16.5 in nucleated red cells but remained stable in nonnucleated red cells.
- Distinct percentage ratios of alpha-globin chains were observed in Hbag2 and Hbac mice for embryonic (EII, EIII) and adult hemoglobins.
- Differences in alpha-globin ratios in nucleated red cells result from combined changes in globin gene transcription and posttranslational affinities.
Conclusions:
- Developmental regulation of alpha-globin ratios occurs primarily in nucleated erythrocytes.
- Globin gene transcription and posttranslational protein interactions are key factors in determining hemoglobin composition during mouse development.