mortality/aging
• 40% of mice have died by 10 months of age compared to 5% of wild-type mice
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renal/urinary system
• there is a five-fold higher increase in the number of renal tubules cells going through apoptosis
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• the urine of some 10-month old mice contains many proteins including transferrin, albumin, and serpine
• by one year of age, 35% of mice have developed proteinuria
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albuminuria
(
J:134208
)
• focal lesions are first observed in the proximal tubules and glomeruli of the outer cortices of mutant mice
• by 3 to 4 months of age, the lesions progress into the inner cortex and medulla and are associated with inflammatory infiltrates and some interstitial fibrosis
• by 5 to 8 months of age, mononuclear inflammatory infiltrates are more extensive and are especially prominent around the vasculature
• by 8 to 12 months of age, the changes in the cortex are moderately to markedly severe and cover the majority of the cortex
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• thickening of the basement membrane of Bowman's capsule at 12 months
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• dilation of Bowman's space is observed at 5-8 months of age
• more pronounced dilation of Bowman's space by 12 months of age
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• glomerular sclerosis by 12 months of age
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• extensive fibrosis is associated with the glomerulonephritis that occurs in these mice
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• kidneys of six month old mice weigh one third less (female) or one half (male) than wild-type mice
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• the kidneys of adult mice are smaller than their wild-type controls and progressively atrophic with age
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• atrophy of the capillary tuft is noted by 12 months of age
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• at P25, affected proximal tubules are atrophic and lined by cuboidal basophilic epithelial cells
• by 12 months, atrophy and loss of the proximal tubules is noted in areas of fibrosis
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• dilation of some cortical and medullary tubules is observed at 5-8 months of age
• tubules are variably dilated by 8-12 months of age
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renal cast
(
J:134208
)
• at 5-8 months of age, several dilated renal tubules contain protein
• many tubules contain protein by 8-12 months of age
|
• mice exhibit progressive degeneration and increased cell death in the kidneys
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pale kidney
(
J:134208
)
• the kidneys of adult mice are paler than their wild-type controls
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• mice develop progressive chronic kidney disease that resembles nephronophthisis and results in renal failure
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behavior/neurological
polydipsia
(
J:134208
)
• increased water consumption at 12 months of age
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homeostasis/metabolism
• mice as young as three months of age exhibit elevated levels of creatinine and these levels increase steadily with age
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• mice as young as three months of age exhibit elevated levels of BUN and these levels increase steadily with age
• mice with high levels of BUN often died within days of analysis
|
• the urine of some 10-month old mice contains many proteins including transferrin, albumin, and serpine
• by one year of age, 35% of mice have developed proteinuria
|
albuminuria
(
J:134208
)
immune system
• focal lesions are first observed in the proximal tubules and glomeruli of the outer cortices of mutant mice
• by 3 to 4 months of age, the lesions progress into the inner cortex and medulla and are associated with inflammatory infiltrates and some interstitial fibrosis
• by 5 to 8 months of age, mononuclear inflammatory infiltrates are more extensive and are especially prominent around the vasculature
• by 8 to 12 months of age, the changes in the cortex are moderately to markedly severe and cover the majority of the cortex
|
cellular
• there is a five-fold higher increase in the number of renal tubules cells going through apoptosis
|