Mouse fetal liver cells lack functional amphotropic retroviral receptors
C Richardson, M Ward, S Podda and A Bank
Department of Genetics and Development, College of Physicians and Surgeons,
Columbia University, New York, NY.
We have been transducing mouse hematopoietic cells with the human MDR1
(MDR) gene in retroviral vectors to determine the optimal conditions for
retroviral gene transfer as a model system for potential human gene
therapy. In these studies, we have demonstrated transduction and expression
of the human MDR gene using ecotropic and amphotropic MDR- retroviral
producer lines. To obtain more mouse hematopoietic cells for detailed
study, mouse fetal liver cells (FLC) have been used for MDR transduction
and expression, and to reconstitute the ablated marrows of live adult mice.
FLC contain hematopoietic cells that have a reconstituting capacity
comparable to that of adult mouse bone marrow cells. However, to our
surprise, FLC can only be transduced with ecotropic retrovirus and not with
amphotropic virus. This restriction of transduction of FLC cannot be
overcome by higher titer virus. The resistance to amphotropic transduction
by FLC may be part of a changing developmental program that results in a
different antigen repertoire on FLC as compared with adult bone marrow
cells.
Volume 84,
Issue 2,
pp. 433-439,
07/15/1994
Copyright © 1994 by The American Society of Hematology