Renal failure in mice with Gsalpha deletion in juxtaglomerular cells.
BACKGROUND
Mice with deletion of Gsalpha in renin-producing cells (RC/FF mice) have been shown to have greatly reduced renin production and lack of responsiveness of renin secretion to acute stimuli. In addition, young RC/FF mice are hypotensive and have a vasopressin-resistant concentrating defect. In the present study we have determined the long-term effect on renal function, blood pressure, and renal pathology in this low renin and diuretic mouse model.


RESULTS
Urine osmolarity of RC/FF mice was decreased in all age groups. GFR measured at 7, 14 and 20 weeks of age declined progressively. Single nephron GFR similarly declined while fractional proximal fluid absorption was maintained. Expression levels of extracellular matrix proteins (collagen I, IV and fibronectin) and alpha-smooth muscle actin were increased in kidneys of RC/FF mice at 20 weeks, and this was accompanied by focal segmental glomerulosclerosis and periglomerular interstitial fibrosis. RC/FF mice showed a progressive reduction of body weight, an increase in urine albumin excretion, and an increase of blood pressure with aging.


CONCLUSIONS
A chronic reduction of renin production in mice may be a risk factor in its own right, and does not protect renal function against the profibrotic influence of a chronically elevated urine flow.
Chen
Limeng
L
National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Md., USA. climeng2000@yahoo.com.cn
Faulhaber-Walter
Robert
R
Wen
Yubing
Y
Huang
Yuning
Y
Mizel
Diane
D
Chen
Min
M
Sequeira Lopez
Maria Luisa
ML
Weinstein
Lee S
LS
Gomez
R Ariel
RA
Briggs
Josephine P
JP
Schnermann
Jurgen
J
D000419:Albuminuria / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D001810:Blood Volume / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D017353:Gene Deletion; D005919:Glomerular Filtration Rate / Q000502:physiology; D007022:Hypotension / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology; D007606:Juxtaglomerular Apparatus / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008817:Mice, Mutant Strains; D009994:Osmolar Concentration; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology*; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology*; D012307:Risk Factors
D015415:Biomarkers; C505409:Casp3 protein, mouse; D053148:Caspase 3; D012083:Renin; D019205:GTP-Binding Protein alpha Subunits, Gs