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Mouse  - and  -Globin Genes: Embryonic Survival, -Thalassemia, and Genetic Background Effects
Aya Leder,
Cathie Daugherty,
Barry Whitney, and
Philip Leder
From the Department of Genetics, Harvard Medical School, Howard Hughes Medical Institute, Boston, MA; and the Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA.
A classical notion regarding the expression of murine embryonic  - and adult  -globin genes holds that there is a switch in globin production from the embryonic to the adult form during fetal development. Our previous in situ hybridization studies challenged this view, since both - and -globin mRNAs can be detected simultaneously in the earliest erythrocyte populations. This finding raises the possibility that -globin production might be wholly or partially redundant in embryos in which the adult -globin is also expressed. To test this possibility, we created a null mutation of the -globin gene using homologous recombination in embryonic stem cells. Many outbred mice homozygous for the -null mutation were able to develop normally, undermining the notion that there is an absolute need for -globin and indicating that -globin alone can serve the survival needs of the fetus. Interestingly, insertion of the PGK-Neo cassette (used to create the null mutation) into the -globin gene appears to influence the expression of the nearby -globin genes, giving rise to reduced -globin production and to an -thalassemia-like syndrome. There is also evidence indicating the strong influence of genetic background on the -null and 1-null phenotypes, both of which are much more severe in the 129/SvEv inbred genetic background. These quantitative differences can potentially be exploited to identify genes important for erythropoiesis.
Blood, Vol. 90 No. 3 (August 1), 1997:
pp. 1275-1282
© 1997 by The American Society of Hematology.
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