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Blood, Vol. 92 No. 5 (September 1), 1998:
pp. 1565-1575
Retroviral Marking of Canine Bone Marrow: Long-Term, High-Level
Expression of Human Interleukin-2 Receptor Common Gamma Chain in
Canine Lymphocytes
Todd Whitwam,
Mark E. Haskins,
Paula S. Henthorn,
Jennifer N. Kraszewski,
Sandra E. Kleiman,
Nancy E. Seidel,
David M. Bodine, and
Jennifer M. Puck
From the Genetics and Molecular Biology Branch, National Human Genome
Research Institute and Laboratory of Cell Biology, Division of Basic
Sciences, National Cancer Institute at the National Institutes of
Health (NIH), Bethesda, MD; and the Department of Genetics, University
of Pennsylvania School of Veterinary Medicine, Philadelphia, PA.
Optimization of retroviral gene transfer into hematopoietic cells of
the dog will facilitate gene therapy of canine X-linked severe combined
immunodeficiency (XSCID) and in turn advance similar efforts to treat
human XSCID. Both canine and human XSCID are caused by defects in the
common  chain, c, of receptors for interleukin-2 and other
cytokines. In this study, normal dogs were given retrovirally
transduced bone marrow cells with and without preharvest mobilization
by the canine growth factors granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF). Harvey
sarcoma virus and Moloney murine leukemia virus constructs were used,
both containing cDNA encoding human c. The Harvey-based vector
transduced into cytokine-primed marrow yielded persistent detectable
provirus in bone marrow and blood and expression of human c on
peripheral lymphocytes. In three dogs, human c expression disappeared after 19 to 34 weeks but reappeared and was sustained, in
one dog beyond 16 months posttransplantation, upon immunosuppression with cyclosporin A and prednisone, with up to 25% of lymphocytes expressing human c. The long-term expression of human c in a high
proportion of normal canine lymphocytes predicts that
retrovirus-mediated gene correction of hematopoietic cells may prove to
be of clinical benefit in humans affected with this XSCID.
This is a US government work. There are no restrictions on its use.
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