Identification of the renal erythropoietin-producing cells using transgenic mice

• Published in: Kidney international Vol. 44; no. 5; pp. 1149 - 1162
• Main Authors: Maxwell, Patrick H., Osmond, Mark K., Pugh, Christopher W., Heryet, Andrew, Nicholls, Lynn G., Tan, Chorh C., Doe, Brendan G., Ferguson, David J.P., Johnson, Martin H., Ratcliffe, Peter J.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 01.11.1993; Nature Publishing
• Subjects: Animals; Antigens, Polyomavirus Transforming - genetics; Antigens, Polyomavirus Transforming - metabolism; Biological and medical sciences; Endocrine kidney. Renin-angiotensin-aldosterone system; Erythropoietin - genetics; Erythropoietin - metabolism; Fundamental and applied biological sciences. Psychology; Genetic Markers; Immunohistochemistry; Kidney - cytology; Kidney - metabolism; Mice; Mice, Transgenic; Microscopy, Immunoelectron; Oligonucleotides - genetics; RNA, Messenger - analysis; Tissue Distribution; Vertebrates: endocrinology; Immunohistochemistry; Erythropoietin; Rodentia; Transgenic animal; Biosynthesis; Experimental study; Glycoprotein hormone; Electron microscopy; Kidney; In vivo; Vertebrata; Mammalia; Urinary system; Mouse
• DOI: 10.1038/ki.1993.362
• ISSN: 0085-2538

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.