Identification of the renal erythropoietin-producing cells using transgenic mice.
Regulation of erythropoietin production by the kidneys is central to the control of erythropoiesis. Uncertainty about the identity of the renal cells involved has been a major obstacle to understanding this mechanism. We have used sequence from the mouse erythropoietin locus to direct expression of a marker gene, SV40 T antigen, to these cells in transgenic mice. The transgenic constructs contained an oligonucleotide marker (Epo-M) or SV40 sequence (Epo-TAg) in the 5' untranslated region of the mouse erythropoietin gene, flanked on each side by 9 and 7.5 kb of DNA from the mouse erythropoietin locus. Anemia-inducible expression of Epo-M and Epo-TAg was observed in the kidney. In one of thirteen lines, homologous integration of Epo-TAg into the mouse erythropoietin locus occurred. In transgenic mice bearing Epo-TAg at homologous and heterologous insertion sites, renal expression was restricted to a population of cells in the interstitium of the cortex and outer medulla. Immunohistochemical characterization by light and electron microscopy shows that these are the fibroblast-like type I interstitial cells.
Maxwell
P H
PH
Department of Pathology.
Osmond
M K
MK
Pugh
C W
CW
Heryet
A
A
Nicholls
L G
LG
Tan
C C
CC
Doe
B G
BG
Ferguson
D J
DJ
Johnson
M H
MH
Ratcliffe
P J
PJ
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000378:metabolism; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism*; D005819:Genetic Markers; D007150:Immunohistochemistry; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron; D009841:Oligonucleotides / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D014018:Tissue Distribution
D000952:Antigens, Polyomavirus Transforming; D005819:Genetic Markers; D009841:Oligonucleotides; D012333:RNA, Messenger; D004921:Erythropoietin