Retrovirus transfer of a bacterial gene into mouse haematopoietic progenitor cells

The haematopoietic system is made up of a hierarchy of cells with different developmental, functional and proliferative capacities. Although cellular diversity appears to arise from the commitment and maturation of stem cells, the molecular basis for this differentiation process is unknown. The introduction of cloned DNA sequences into haematopoietic progenitor cells would provide a novel approach for studying this differentiating in vivo system. One laboratory has reported DNA-mediated transfer of genes into mouse bone marrow cells. However, retroviruses offer a number of advantages over DNA-mediated gene transfer procedures, including high efficiency infection of a wide range of cell types in vitro and in vivo, stable and low copy integration into the host chromosome, and a defined integrated provirus structure. For these reasons recombinant DNA techniques have been utilized to construct high efficiency retrovirus vectors expressing foreign genes. We demonstrate here, using such a retrovirus vector, the transfer of a dominant selectable drug-resistance gene into defined classes of mouse haematopoietic progenitor cells. These observations should facilitate the development of molecular genetic approaches to fundamental and clinical problems in haematopoiesis.