mortality/aging
• only 10% of mice survived to 6 weeks of age
• 90% of mice were euthanized at 4-5 weeks of age due to end stage renal failure and nephrotic syndrome
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behavior/neurological
• mice become less physically active at 3 weeks of age
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growth/size/body
• at 6 weeks of age, mice are smaller than control littermates
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homeostasis/metabolism
• mice develop severe proteinuria by 6 weeks of age
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albuminuria
(
J:135414
)
• albuminuria is already evident at P1
• marked albuminuria is noted at 6 weeks of age
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renal/urinary system
• a significant increase in podocyte apoptosis is detected at P10 and P21 by TUNEL analysis
• at P21, mice exhibit about one-third of the podocyte number found in control littermates, as quantified in EM sections
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• mice develop severe proteinuria by 6 weeks of age
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albuminuria
(
J:135414
)
• albuminuria is already evident at P1
• marked albuminuria is noted at 6 weeks of age
|
• mice develop end stage kidney disease with pathological changes in the glomeruli and tubulo-interstitium
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• at 6 weeks of age, many Bowmans capsules are either empty or contain partially degenerated glomeruli
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• foot process effacement is first noted at E15.5
• extensive foot process effacement is noted at P10 and progresses by P21
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• early segmental splitting of the glomerular basement membrane (GBM) is first noted at P10 and progresses by P21
• however, normal GBM morphogenesis is noted at E15.5 and at P1
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• at P21, mice exhibit degeneration of the capillary loops and mesangium with little glomerulosclerosis
• at 6 weeks of age, mice exhibit dilated glomerular capillaries and glomerular disintegration
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• by P21, mice exhibit degeneration of the capillary loops
• however, normal glomerular capillary morphogenesis is noted at E15.5 and at P1
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• at P10, some glomeruli display segmentally "ballooned" capillary lumens; more "ballooned" capillary loops are noted at 3 weeks of age
• at 6 weeks of age, mice exhibit dilated glomerular capillaries
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• mesangium hypercellularity is observed by 3 weeks of age
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• increased mesangial matrix with focal defects is noted at 3 weeks, indicating mesangial injury
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• multiple cytoplasmic vacuoles are first noted in mesangial cells at P10
• by P21, mice exhibit degeneration of the mesangium with little glomerulosclerosis
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• at P10, mice exhibit multiple cytoplasmic vacuoles within the tubular epithelial cells
• flattened epithelial cells with extensive proteinaceous tubular casts are noted at 6 weeks of age
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small kidney
(
J:135414
)
• at 6 weeks of age, end stage kidneys are smaller than those of age-matched control mice
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• dilated renal tubules containing hyaline material are observed at 6 weeks of age
• tubular dilatation is first evident at P10 and increased by 3 weeks of age
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renal cast
(
J:135414
)
• extensive proteinaceous tubular casts are noted at 6 weeks of age
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pale kidney
(
J:135414
)
• at 6 weeks of age, end stage kidneys are paler than those of age-matched control mice
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cardiovascular system
• by P21, mice exhibit degeneration of the capillary loops
• however, normal glomerular capillary morphogenesis is noted at E15.5 and at P1
|
• at P10, some glomeruli display segmentally "ballooned" capillary lumens; more "ballooned" capillary loops are noted at 3 weeks of age
• at 6 weeks of age, mice exhibit dilated glomerular capillaries
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cellular
• mesangium hypercellularity is observed by 3 weeks of age
|
• a significant increase in podocyte apoptosis is detected at P10 and P21 by TUNEL analysis
• at P21, mice exhibit about one-third of the podocyte number found in control littermates, as quantified in EM sections
|