Promoter elements of vav drive transgene expression in vivo throughout the hematopoietic compartment.
To develop a method for targeting expression of genes to the full hematopoietic system, we have used transgenic mice to explore the transcriptional regulation of the vav gene, which is expressed throughout this compartment but rarely outside it. Previously, we showed that a cluster of elements surrounding its promoter could drive hematopoietic-specific expression of a bacterial lacZ reporter gene, but the expression was confined to lymphocytes and was sporadically silenced. Those limitations are ascribed here to the prokaryotic 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 nonhematopoietic cell types. In multiple lines, hCD4 appeared on most, if not all, B and T lymphocytes, granulocytes, monocytes, megakaryocytes, eosinophils, and nucleated erythroid cells. Moreover, high levels appeared on both lineage-committed progenitors and the more primitive preprogenitors. In the fetus, expression was evident in erythroid cells of the definitive but not the primitive type. These results indicate that a prokaryotic sequence can inactivate a transcription unit and that the vav promoter region constitutes a potent transgenic vector for the entire definitive hematopoietic compartment.
Ogilvy
S
S
The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Metcalf
D
D
Gibson
L
L
Bath
M L
ML
Harris
A W
AW
Adams
J M
JM
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D015704:CD4 Antigens / Q000032:analysis / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins; D005434:Flow Cytometry; D017930:Genes, Reporter; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D008214:Lymphocytes / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav; D011993:Recombinant Fusion Proteins / Q000032:analysis; D015183:Restriction Mapping
D015704:CD4 Antigens; D018797:Cell Cycle Proteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D011993:Recombinant Fusion Proteins; C496618:VAV1 protein, human; C496619:Vav1 protein, mouse