Analysis Tools
mortality/aging
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• mice start to die prematurely at 15 weeks and no mice survive past 20 weeks of age due to renal failure
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homeostasis/metabolism
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• blood urea nitrogen levels are normal at 8 weeks of age but become significantly increased at 16 weeks of age
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albuminuria
(
J:300239
)
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• although no significant albuminuria is detectable at 8 weeks of age, mice exhibit massive albuminuria at 12 weeks that further progresses by 16 weeks of age
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• following induction of glomerulonephritis at 4 weeks of age using a nephrotoxic serum that binds to the GBM, mice exhibit no differences in albuminuria or BUN levels within 48 h after induction but develop significantly more sclerotic lesions and renal casts than littermate controls at 14 days post-induction, indicating increased susceptibility to kidney glomerular injury
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renal/urinary system
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• occasionally, podocytes show nuclear changes suggesting an apoptotic process
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albuminuria
(
J:300239
)
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• although no significant albuminuria is detectable at 8 weeks of age, mice exhibit massive albuminuria at 12 weeks that further progresses by 16 weeks of age
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• EM revealed significant foot process effacement at 8 weeks, but not at 4 weeks, of age
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• at 16 weeks of age, areas of GBM are not covered by podocytes indicating podocyte loss
• immunofluorescence analysis revealed that podocyte markers nephrin, synaptopodin and WT1 show progressive loss of signal starting at 8 weeks with only few glomeruli exhibiting positivity by 16 weeks; quantification of WT1 nuclei confirmed podocyte loss at both 12 and 16 weeks
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• EM revealed progressive vesicular lesions in podocytes; large vesicular structures are negative for lipids as shown by oil red staining
• vesicular structures are frequently seen in podocyte cytoplasm at 12 weeks of age; occasionally, vesicles obstruct podocyte nuclei
• vesicular membranes lack the electron-dense glycocalyx that is present on the podocyte plasma membrane
• vacuole-like structures show no connections to Bowmans space at 12-16 weeks of age
• immunofluorescence staining for vesicular markers revealed that lysosomal marker LAMP2 is strongly upregulated in podocytes at 12 weeks, but not at 8 weeks of age, as shown by double-labeling with WT1 and CD31; endocytosis marker caveolin is also upregulated in LAMP2-positive cells
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• at 12 weeks of age, glomeruli exhibit focal segmental sclerosis and large empty vacuole-like structures in podocytes
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• focal segmental sclerosis is observed at 12 weeks of age; most glomeruli are completely sclerotic by 16 weeks of age
• following induction of glomerulonephritis at 4 weeks of age using a nephrotoxic serum that binds to the GBM, mice develop significantly more sclerotic lesions than littermate controls at 14 days post-induction
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• interstitial fibrosis is observed at 12 weeks of age
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• renal tubular atrophy is observed at 16 weeks of age
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• dilated renal tubules with hyaline casts are detected at 12 weeks of age, with more pronounced dilation seen by 16 weeks of age
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renal cast
(
J:300239
)
|
• dilated renal tubules with hyaline casts are detected at 12 weeks of age, with more hyaline casts seen by 16 weeks of age
• following induction of glomerulonephritis at 4 weeks of age using a nephrotoxic serum that binds to the GBM, mice develop significantly more renal casts than littermate controls at 14 days post-induction
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• all mice die by 20 weeks of age due to renal failure
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cellular
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• occasionally, podocytes show nuclear changes suggesting an apoptotic process
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