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Blood, Vol. 94 No. 6 (September 15), 1999:
pp. 1855-1863
Promoter Elements of vav Drive Transgene Expression In Vivo
Throughout the Hematopoietic Compartment
Sarah Ogilvy,
Donald Metcalf,
Leonie Gibson,
Mary L. Bath,
Alan W. Harris, and
Jerry M. Adams
From The Walter and Eliza Hall Institute of Medical Research, Royal
Melbourne Hospital, Victoria, Australia.
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.
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