RESUMEN
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.
Asunto(s)
Endotelina-1/genética , Glomeruloesclerosis Focal y Segmentaria/genética , Hipertensión/genética , Enfermedades Renales Quísticas/genética , Nefritis Intersticial/genética , Animales , Presión Sanguínea , Northern Blotting , Constitución Corporal , Endotelina-1/sangre , Endotelina-1/metabolismo , Femenino , Regulación de la Expresión Génica , Tasa de Filtración Glomerular , Glomeruloesclerosis Focal y Segmentaria/etiología , Glomeruloesclerosis Focal y Segmentaria/patología , Humanos , Hipertensión/etiología , Hibridación in Situ , Enfermedades Renales Quísticas/etiología , Enfermedades Renales Quísticas/patología , Masculino , Ratones , Ratones Transgénicos , Nefritis Intersticial/etiología , Nefritis Intersticial/patología , Tamaño de los Órganos , Potasio/orina , Proteinuria/orina , Arteria Renal/patología , Sodio/orinaRESUMEN
Transgenic mice expressing the human endothelin-1 (ET-1) were generated. These mice develop glomerulosclerosis, interstitial fibrosis, and renal cysts but not hypertension. Consequently, a progressive decrease in renal blood flow and/or glomerular filtration rate was observed, demonstrated by altered creatinine clearance and by magnetic resonance imaging. These genetically altered transgenic mice provide an interesting animal model in which to elucidate the role of ET-1 in the modulation of renal hemodynamics and glomerular and tubule functions.