title: Endothelin-1 transgenic mice develop glomerulosclerosis, interstitial fibrosis, and renal cysts but not hypertension.
abstract: The human endothelin-1 (ET-1) gene under the control of its natural promoter was transferred into the germline of mice. The transgene was expressed predominantly in the brain, lung, and kidney. Transgene expression was associated with a pathological phenotype manifested by signs such as age-dependent development of renal cysts, interstitial fibrosis of the kidneys, and glomerulosclerosis leading to a progressive decrease in glomerular filtration rate. This pathology developed in spite of only slightly elevated plasma and tissue ET-1 concentrations. Blood pressure was not affected even after the development of an impaired glomerular filtration rate. Therefore, these transgenic lines provide a new blood pressure-independent animal model of ET-1-induced renal pathology leading to renal fibrosis and fatal kidney disease.
authors.affiliation: Department of Nephrology, Charité, Humboldt University of Berlin, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Hocher
authors.forename: C
authors.initials: C
authors.lastname: Thöne-Reineke
authors.forename: P
authors.initials: P
authors.lastname: Rohmeiss
authors.forename: F
authors.initials: F
authors.lastname: Schmager
authors.forename: T
authors.initials: T
authors.lastname: Slowinski
authors.forename: V
authors.initials: V
authors.lastname: Burst
authors.forename: F
authors.initials: F
authors.lastname: Siegmund
authors.forename: T
authors.initials: T
authors.lastname: Quertermous
authors.forename: C
authors.initials: C
authors.lastname: Bauer
authors.forename: H H
authors.initials: HH
authors.lastname: Neumayer
authors.forename: W D
authors.initials: WD
authors.lastname: Schleuning
authors.forename: F
authors.initials: F
authors.lastname: Theuring
mesh_terms: D000818:Animals; D001794:Blood Pressure; D015152:Blotting, Northern; D001824:Body Constitution; D019332:Endothelin-1 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D005919:Glomerular Filtration Rate; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000235:genetics*; D017403:In Situ Hybridization; D052177:Kidney Diseases, Cystic / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009395:Nephritis, Interstitial / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D009929:Organ Size; D011188:Potassium / Q000652:urine; D011507:Proteinuria / Q000652:urine; D012077:Renal Artery / Q000473:pathology; D012964:Sodium / Q000652:urine
chemical_list: D019332:Endothelin-1; D012964:Sodium; D011188:Potassium