In:
Blood, American Society of Hematology, Vol. 90, No. 3 ( 1997-08-01), p. 1275-1282
Abstract:
A classical notion regarding the expression of murine embryonic ζ- and adult α-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 ζ- and α-globin mRNAs can be detected simultaneously in the earliest erythrocyte populations. This finding raises the possibility that ζ-globin production might be wholly or partially redundant in embryos in which the adult α-globin is also expressed. To test this possibility, we created a null mutation of the ζ-globin gene using homologous recombination in embryonic stem cells. Many outbred mice homozygous for the ζ-null mutation were able to develop normally, undermining the notion that there is an absolute need for ζ-globin and indicating that α-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 ζ-globin gene appears to influence the expression of the nearby α-globin genes, giving rise to reduced α-globin production and to an α-thalassemia–like syndrome. There is also evidence indicating the strong influence of genetic background on the ζ-null and α1-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.
Type of Medium:
Online Resource
ISSN:
1528-0020
,
0006-4971
DOI:
10.1182/blood.V90.3.1275.1275_1275_1282
Language:
English
Publisher:
American Society of Hematology
Publication Date:
1997
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
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