title: Expression of a homologously recombined erythopoietin-SV40 T antigen fusion gene in mouse liver: evidence for erythropoietin production by Ito cells.
abstract: 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.
authors.affiliation: Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
authors.forename: P H
authors.initials: PH
authors.lastname: Maxwell
authors.forename: D J
authors.initials: DJ
authors.lastname: Ferguson
authors.forename: M K
authors.initials: MK
authors.lastname: Osmond
authors.forename: C W
authors.initials: CW
authors.lastname: Pugh
authors.forename: A
authors.initials: A
authors.lastname: Heryet
authors.forename: B G
authors.initials: BG
authors.lastname: Doe
authors.forename: M H
authors.initials: MH
authors.lastname: Johnson
authors.forename: P J
authors.initials: PJ
authors.lastname: Ratcliffe
mesh_terms: D000740:Anemia / Q000378:metabolism; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000032:analysis / Q000235:genetics*; D004921:Erythropoietin / Q000235:genetics*; D015870:Gene Expression; D000860:Hypoxia / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron; D009928:Organ Specificity; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins
chemical_list: D000952:Antigens, Polyomavirus Transforming; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D004921:Erythropoietin