Promoter elements of vav drive transgene expression in vivo throughout thehematopoietic compartment

To develop a method for targeting expression of genes to the full hematopoi etic system, we have used transgenic mice to explore the transcriptional re gulation of the vav gene, which is expressed throughout this compartment bu t rarely outside it. Previously, we showed that a cluster of elements surro unding its promoter could drive hematopoietic-specific expression of a bact erial lacZ reporter gene, but the expression was confined to lymphocytes an d was sporadically silenced. Those limitations are ascribed here to the pro karyotic reporter gene. With a human CD4 (hCD4) cell surface reporter, the vav promoter elements drove expression efficiently and stably in virtually all nucleated cells of adult hematopoietic tissues but not notably in nonhe matopoietic cell types. in multiple lines, hCD4 appeared on most, if not al l, B and T lymphocytes, granulocytes, monocytes, megakaryocytes, eosinophil s, and nucleated erythroid cells. Moreover, high levels appeared on both li neage-committed progenitors and the more primitive preprogenitors. In the f etus, expression was evident in erythroid cells of the definitive but not t he primitive type. These results indicate that a prokaryotic sequence can i nactivate a transcription unit and that the vav promoter region constitutes a potent transgenic vector for the entire definitive hematopoietic compart ment, (C) 1999 by The American Society of Hematology.