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Expression of a homologously recombined erythopoietin-SV40 T antigen fusion
gene in mouse liver: evidence for erythropoietin production by Ito cells
PH Maxwell, DJ Ferguson, MK Osmond, CW Pugh, A Heryet, BG Doe, MH Johnson and PJ Ratcliffe
Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
We have obtained transgenic mice in which an erythropoietin-SV40 virus T
antigen fusion gene is homologously recombined into the native Epo locus.
This gene is expressed in a tissue-specific manner closely resembling that
of the native Epo gene. Immunohistochemical detection of SV40 T antigen has
been used to characterize the hepatic cell populations expressing the
transgene. In mice stimulated by anaemia or hypobaric hypoxia, SV40 T
antigen was demonstrated in two liver cell populations: a subset of
hepatocytes and a nonparenchymal cell type. Immunohistochemical and
ultrastructural characterization of these cells by light and electron
microscopy showed the nonparenchymal cell type to be the Ito cells, which
lie in a persinusoidal position within the space of Disse. We therefore
conclude that Ito cells are the nonhepatocytic source of liver Epo
production. These cells show many similarities to the Epo-producing
fibroblastoid interstitial cells of the kidney.
Volume 84,
Issue 6,
pp. 1823-1830,
09/15/1994
Copyright © 1994 by The American Society of Hematology
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