Synthesis of Functional Human Hemoglobin in Transgenic Mice
Human $\alpha $- and $\beta $-globin genes were separately fused downstream of two erythroid-specific deoxyribonuclease (DNase) I super-hypersensitive sites that are normally located 50 kilobases upstream of the human $\beta $-globin gene. These two constructs were coinjected into fertilized mouse e...
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Published in | Science (American Association for the Advancement of Science) Vol. 245; no. 4921; pp. 971 - 973 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Washington, DC
The American Association for the Advancement of Science
01.09.1989
American Association for the Advancement of Science |
Subjects | |
Online Access | Get full text |
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Summary: | Human $\alpha $- and $\beta $-globin genes were separately fused downstream of two erythroid-specific deoxyribonuclease (DNase) I super-hypersensitive sites that are normally located 50 kilobases upstream of the human $\beta $-globin gene. These two constructs were coinjected into fertilized mouse eggs, and expression was analyzed in transgenic animals that developed. Mice that had intact copies of the transgenes expressed high levels of correctly initiated human $\alpha $- and $\beta $-globin messenger RNA specifically in erythroid tissue. An authentic human hemoglobin was formed in adult erythrocytes that when purified had an oxygen equilibrium curve identical to the curve of native human hemoglobin A (Hb A). Thus, functional human hemoglobin can be synthesized in transgenic mice. This provides a foundation for production of mouse models of human hemoglobinopathies such as sickle cell disease. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0036-8075 1095-9203 |
DOI: | 10.1126/science.2772649 |