Expression of a homologously recombined erythopoietin-SV40 T antigen fusion gene in mouse liver: evidence for erythropoietin production by Ito cells.
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.
Maxwell
P H
PH
Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
Ferguson
D J
DJ
Osmond
M K
MK
Pugh
C W
CW
Heryet
A
A
Doe
B G
BG
Johnson
M H
MH
Ratcliffe
P J
PJ
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
D000952:Antigens, Polyomavirus Transforming; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D004921:Erythropoietin