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A Common Human  Globin Splicing Mutation Modeled in Mice
Jada Lewis,
Baoli Yang,
Ronald Kim,
Halina Sierakowska,
Ryszard Kole,
Oliver Smithies, and
Nobuyo Maeda
From the Curriculum of Genetics and Molecular Biology, University of
North Carolina, Chapel Hill; the Department of Pathology and Laboratory
of Medicine, University of North Carolina, Chapel Hill; the Lineberger
Comprehensive Cancer Center and Department of Pharmacology, University
of North Carolina, Chapel Hill, NC.
The  IVS-2-654 C T mutation accounts for approximately
20% of thalassemia mutations in southern China; it causes aberrant RNA splicing and leads to 0 thalassemia. To provide an
animal model for testing therapies for correcting splicing defects, we
have used the "plug and socket" method of gene targeting in
murine embryonic stem cells to replace the two (cis) murine
adult globin genes with a single copy of the human IVS-2-654
gene. No homozygous mice survive postnatally. Heterozygous mice
carrying this mutant gene produce reduced amounts of the mouse globin chains and no human globin, and have a moderate form of thalassemia. The heterozygotes show the same aberrant splicing as their
human counterparts and provide an animal model for testing therapies to
correct splicing defects at either the RNA or DNA level.
Blood, Vol. 91 No. 6 (March 15), 1998:
pp. 2152-2156
© 1998 by The American Society of Hematology.
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