Although the hematopoietic stem cell is an attractive target for gene transfer, little is known about its biology in vivo in large animals (including humans). We have studied the in vivo behavior of hematopoietic stem cells in glucose-6-phosphate dehydrogenase heterozygous (female Safari) cats, and demonstrated that clonal instability persists for up to 4.5 years after autologous marrow transplantation. This contrasts with the 2-6 months of clonal disequilibrium reported in comparable murine studies. Our data also suggest that hematopoietic stem cells do not self-renew more than once every 3 weeks. These data may have relevance for strategies to optimize gene therapy in large animals and, by extension, in humans.

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