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Novel metabolism of several beta zero‐thalassemic beta‐globin mRNAs in the erythroid tissues of transgenic mice.
Author(s) -
Lim S.,
Mullins J.J.,
Chen C.M.,
Gross K.W.,
Maquat L.E.
Publication year - 1989
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1989.tb08401.x
Subject(s) - biology , beta (programming language) , globin , transgene , genetically modified mouse , microbiology and biotechnology , beta thalassemia , genetics , gene , thalassemia , computer science , programming language
Mice that are transgenic for human beta zero‐thalassemic beta‐globin alleles were generated in order to study how beta zero‐thalassemic mutations affect beta‐globin RNA metabolism in erythroid tissues. Three thalassemic alleles were studied, each of which harbors either a frameshift or a nonsense mutation. These mutations result in the premature termination of beta‐globin mRNA translation and an abnormally low level of beta‐globin mRNA in the peripheral blood of thalassemic patients. Comparative studies of mice that express any of the beta zero‐thalassemic transgenes with mice that express a normal human beta‐globin transgene demonstrated that all three thalassemic mRNAs are metabolized in erythroid tissues abnormally. RNA blotting and S1 nuclease transcript mapping revealed for each thalassemic transgene that (i) the full‐length mRNA is abnormally short‐lived and (ii) in addition to full‐length mRNA, three more stable yet smaller RNAs are present. These smaller RNAs are polyadenylated and lack the mRNA 5′ end.