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 245 bp of 5 -Flanking Region From the Human Platelet
Factor 4 Gene Is Sufficient to Drive Megakaryocyte-Specific
Expression In Vivo
Zheng Cui,
Michael P. Reilly,
Saul Surrey,
Elias Schwartz, and
Steven E. McKenzie
From the Children's Hospital of Philadelphia, Philadelphia, PA;
Departments of Pediatrics and Research, duPont Hospital for Children,
Wilmington, DE; and Thomas Jefferson University, Philadelphia, PA.
Platelet factor 4 (PF4) serves as a lineage-specific marker of
megakaryocyte development. We previously identified two positively acting sequences in the human platelet factor 4 (hPF4) gene promoter that synergized to drive high-level luciferase reporter gene expression in vitro. Using portions of the hPF4 5 -flanking region linked to
the lacZ reporter gene, we observed in this investigation that constructs with  245 bp of 5-flanking region were more active than constructs with 2 kb of 5-flanking region in vitro. We created two independent transgenic mouse lines with a 245-bp hPF4/lacZ construct. Cells from these mice were tested for
 -galactosidase (-gal) expression at the mRNA level
by Northern blot and semiquantitative reverse transcription polymerase
chain reaction (RT-PCR) and at the protein level by
immunohistochemistry assay. Mice from one line showed -gal
expression specifically in all megakaryocytes of all ploidy classes
from bone marrow and in platelets. Expression level was comparable to
that driven by the 1.1-kb rat PF4 promoter in other transgenic mouse
lines. Those in the second line showed no -gal expression in
megakaryocytes, platelets, or any of the eight organs tested. The
245-bp hPF4 promoter is capable of driving reporter gene expression
in a megakaryocyte-specific manner in transgenic mice. The small size
of this megakaryocyte-specific promoter is compatible with that
required in some viral vectors and may provide a model for targeting
gene expression to megakaryocytes.
Blood, Vol. 91 No. 7 (April 1), 1998:
pp. 2326-2333
© 1998 by The American Society of Hematology.
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