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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.


Journal article



Publication Date





1823 - 1830


Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.


Liver, Animals, Mice, Transgenic, Mice, Anemia, Erythropoietin, Antigens, Polyomavirus Transforming, Recombinant Fusion Proteins, RNA, Messenger, Microscopy, Immunoelectron, Immunohistochemistry, Organ Specificity, Gene Expression, Phenotype, Hypoxia