Analysis Tools
mortality/aging
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• increased mortality following renal ischemia/reperfusion procedure (1 of 8) compared to wild-type (0 of 10) and sham controls (0 of 7)
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• mice have much shorter lifespan than wild-type; 909 days (wt) vs 755 days (mutant)
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• following embryonic salt stress (high-salt, 5% NaCl intake), only 38% of progeny from heterozygous matings survive past the first week of life, unlike in unstressed homozygotes or salt-loaded wild-type control mice where survival is 84% or greater
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renal/urinary system
 N |
• under physiological conditions, 8-wk-old male homozygotes exhibit normal kidney weight, renal plasma flow, glomerular filtration rate (GFR), renal vascular resistance (RVR), urine osmolarity, and urine sodium and potassium excretion relative to wild-type controls
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• under physiological conditions, 8-wk-old male homozygotes display significantly reduced nitrite excretion relative to wild-type controls
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• in the kidney of postischimic mice there is more oxidative nuclear and mitochondrial DNA modification than in wild-type but not as severe as in the Bdkrb1/Bdkrb2 double knockout
• apoptosis rates are increased in postischemic mice compared to in wild-type but not as much as in the Bdkrb1/Bdkrb2 double knockout
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• at P2, salt-stressed homozygotes display a disorganized renal cortex
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• at P2, salt-stressed homozygotes display areas of tubular microcysts
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• the % of juxtaglomerular apparatuses expressing rennin is significantly lower than in homozygotes maintained on normal salt intake
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• at P2, salt-stressed homozygotes display suppressed immunoreactive renin in juxtaglomerular cells
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• at P2, the cortical medullary rays are either poorly developed or missing in salt-stressed mutants, unlike in control mice
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• following embryonic salt stress, E16 homozygotes display abnormal nephrogenesis with focal areas of tubular ectasia
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• at P2, salt-stressed homozygotes display renal dysplasia in the distal nephron, unlike control mice
• increased susceptibility to salt-induced nephropathy is intrinsic to the fetus; homozygous offspring from heterozygous parents display the same renal phenotype as offspring from homozygous null parents
• chronic antihypertensive therapy (hydralazine; birth to P20) does not modify the severity of renal defects
• Background Sensitivity: a significantly higher % of homozygotes develop salt-induced renal abnormalities on a congenic C57BL/6J background (84%) compared to a mixed 129 x C57BL/6 (F4) genetic background (57%)
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• salt-stressed homozygotes display dilated Bowman's space, unlike control mice
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• at P2, salt-stressed homozygotes display primitive glomeruli, unlike control mice; however, the number of mature glomeruli and glomerular generations remain normal
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• under physiological conditions, 8-wk-old male homozygotes show a reduced glomerular tuft area, caused by a ~20% reduction in glomerular capillary surface area relative to wild-type controls
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• at P2, salt-stressed homozygotes display renal tubule dysplasia of ureteric bud origin
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• at P2, salt-stressed homozygotes display aberrations in epithelial nephrogenesis involving both kidneys
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• postischimic mice have more severe histologial changes in renal proximal tubules than in wild-type but not as severe as in the double knockout
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• at P2, salt-stressed homozygotes display tubular ectasia
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• 8-wk-old male homozygotes show a 50% decrease in basal cGMP levels in isolated glomeruli relative to wild-type controls
• following stimulation with calcium ionophore A23187, mutant glomeruli exhibit a significantly lower cGMP production relative to wild-type controls, suggesting an impaired NO-cGMP pathway
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homeostasis/metabolism
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N |
• under physiological conditions, 8-wk-old male homozygotes display normal urine osmolarity, and urine sodium and potassium excretion relative to wild-type controls
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• postischimic mice have increased plasma creatinine compared to wild-type but not as much as in the Bdkrb1/Bdkrb2 double knockout
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• fasting plasma nitrite/nitrate levels are decreased compared to normal
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• postischimic mice have increased plasma urea nitrogen compared to wild-type but not as much as in the Bdkrb1/Bdkrb2 double knockout
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• under physiological conditions, 8-wk-old male homozygotes display significantly reduced nitrite excretion relative to wild-type controls
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cellular
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• mutant mice show greater mitochondrial damage than wild-type at 12 months of age
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endocrine/exocrine glands
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• mutant males display some pigmented vacuoles in Leydig cells in the testes at 12 months of age
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reproductive system
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• mutant males display some pigmented vacuoles in Leydig cells in the testes at 12 months of age
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skeleton
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• mutants have significantly reduced bone density compared to wild-type
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behavior/neurological
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N |
• under physiological conditions, 8-wk-old male homozygotes exhibit normal water and food intake relative to wild-type controls
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cardiovascular system
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N |
• under physiological conditions, 8-wk-old male homozygotes display normal blood pressure, heart rate, renal plasma flow, and renal vascular resistance relative to wild-type controls
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• under physiological conditions, 8-wk-old male homozygotes show a reduced glomerular tuft area, caused by a ~20% reduction in glomerular capillary surface area relative to wild-type controls
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growth/size/body
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• at P2, salt-stressed homozygotes display areas of tubular microcysts
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