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Human adenosine deaminase expression in mice
KA Moore, FA Fletcher, DK Villalon, AE Utter and JW Belmont
Institute for Molecular Genetics, Baylor College of Medicine, Houston, TX
77030.
A replication defective retroviral vector containing a human adenosine
deaminase (hADA) cDNA was produced by GP + E-86 packaging cells at high
titer. We report long-term expression of hADA in the hematopoietic tissues
of mice transplanted with bone marrow cells infected by in vitro
co-cultivation with vector producing cells. Western analysis using an
hADA-specific antibody allowed detection of the protein in the peripheral
blood of all 37 transplanted mice for at least 9 weeks. Sixty-eight percent
of the animals continued to express hADA in one or more of their
hematopoietic tissues for the experimental period, and hADA was found in
both spleen colonies and tissues of secondary recipients. There was
provirus integration and expression in myeloid, erythroid, and lymphoid
cell lineages, indicating extensive repopulation by the progeny of infected
stem cells. The vector did not contain a selectable marker, and the
infected stem cells did not have a competitive in vivo advantage.
Nevertheless, we observed consistent gene transfer into hematopoietic stem
cells and long-term expression of a human gene product in their progeny.
Volume 75,
Issue 10,
pp. 2085-2092,
05/15/1990
Copyright © 1990 by The American Society of Hematology
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