Analysis Tools
mortality/aging
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• contrary to previous findings (J:25284), homozygotes generated from F1 intercrosses are obtained at the expected Mendelian frequency
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cardiovascular system
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• homozygotes exhibit thickened intrarenal arteries and arterioles as a result of medial hyperplasia
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• thickened and hyperplastic renal arteries are observed
• inflammatory cells can be seen around the renal arteries with some infiltration into the vessel wall
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• homozygotes exhibit an increase in average pulse rates (676 12 beats/min) relative to wild-type (626 16 beats/min) or heterozygous mutant mice (625 8 beats/min)
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• homozygotes exhibit a significantly reduced average systolic blood pressure (73.3 1.7 mm Hg) relative to wild-type (110.1 1.9 mm Hg) or heterozygous mutant mice (107.3 1.6 mm Hg)
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renal/urinary system
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• homozygotes exhibit thickened intrarenal arteries and arterioles as a result of medial hyperplasia
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• thickened and hyperplastic renal arteries are observed
• inflammatory cells can be seen around the renal arteries with some infiltration into the vessel wall
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• following water deprivation, homozygotes display a reduction in electrolyte concentration, with a significantly lower urinary sodium to potassium ratio
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• following water deprivation, homozygotes produce ~50% of the total aldosterone levels found in the urine of wild-type mice
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• following water deprivation, homozygotes exhibit increased potassium excretion relative to wild-type mice
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• when water is freely accessible, homozygotes exhibit a slightly lower average urine osmolarity (770 30 mOSM/kg ) relative to wild-type mice (1070 60 mOSM/kg)
• following water deprivation, homozygotes produce a higher (2x) volume of urine that is <50% as concentrated (1300 10 mOSM/kg) than that of wild-type mice (3000 300 mOSM/kg)
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• regions of inflammatory infiltrate are seen at the cortical medullary junction
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• regions of inflammatory infiltrate are seen at the cortical medullary junction
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• mutant kidneys display papillary atresia
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• mutant kidneys display renal papillary atrophy
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• mutant kidneys display a thinned medulla
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• mutant kidneys display dilated renal calyses
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• homozygotes display dilation of the renal pelvis and calyces
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• homozygous mutant kidneys are ~75% of the mass of wild-type kidneys
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• when water is freely accessible, homozygotes show a 2-fold increase in urinary output relative to wild-type mice
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reproductive system
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• male homozygotes sire significantly smaller litters than wild-type males (3.3 1.4 vs 9.7 1.5 pups per litter, respectively)
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• male homozygotes display reduced fertility, despite normal testis histology and normal sperm number, morphology, and motility
• in contrast, female homozygotes are fertile and produce normal litter sizes
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homeostasis/metabolism
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• homozygotes display significantly increased plasma creatinine levels (0.56 0.06 mg/dl) relative to wild-type mice (0.30 0.04 mg/dl)
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• following water deprivation, homozygotes display a reduction in electrolyte concentration, with a significantly lower urinary sodium to potassium ratio
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• following water deprivation, homozygotes produce ~50% of the total aldosterone levels found in the urine of wild-type mice
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• following water deprivation, homozygotes exhibit increased potassium excretion relative to wild-type mice
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• when water is freely accessible, homozygotes exhibit a slightly lower average urine osmolarity (770 30 mOSM/kg ) relative to wild-type mice (1070 60 mOSM/kg)
• following water deprivation, homozygotes produce a higher (2x) volume of urine that is <50% as concentrated (1300 10 mOSM/kg) than that of wild-type mice (3000 300 mOSM/kg)
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immune system
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• regions of inflammatory infiltrate are seen at the cortical medullary junction
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