Analysis Tools
mortality/aging
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• mice become moribund at 10 months of age with advanced decline of kidney function
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• untreated mice exhibit 50% mortality by 10 months of age; median survival is 306 days
• treatment with 2,4-Dihydroxybenzoic acid (2,4-diHB, an analog of a CoQ precursor molecule) prevents disease progression, resulting in normal survival range
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behavior/neurological
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• hunched posture at >10 months of age
• treatment with 2,4-diHB ameliorates physical condition
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integument
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• scruffy fur at >10 months of age
• treatment with 2,4-diHB ameliorates physical condition
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renal/urinary system
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• obliteration of glomerular capillary lumens at 10 months of age
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• males are more susceptible to proteinuria than females
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albuminuria
(
J:278754
)
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• 7.4-fold increase in the albumin-to-creatinine ratio at 5 months of age
• up to 46.9-fold increase in albuminuria at 10 months of age
• treatment with 2,4-diHB protects mice from developing proteinuria
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• podocytes appear to contain abnormal mitochondria characterized by hyperproliferation and increased size at >10 months of age
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• podocyte foot process effacement first observed at 5 months of age, becoming more severe by 10 months of age
• treatment with 2,4-diHB results in normal foot process morphology
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• significantly reduced number of filtration slit units per micrometer of basement membrane at >10 months of age
• treatment with 2,4-diHB results in normal filtration slit morphology
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• significant reduction in expression of podocyte-specific proteins and number of WT1+ podocytes at >10 months of age, suggesting depletion of podocytes
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• significant thickening of the glomerulus basement membrane at 10, but not at 5, months of age
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• mild focal glomerular sclerosis at 5 months of age, becoming more severe with an increased number of sclerotic glomeruli (93.87%) by 10 months of age
• treatment with 2,4-diHB mitigates the sclerotic phenotype (4.95%) and results in normal histologic kidney morphology
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• significantly increased expression of fibrotic markers (alphaSMA, desmin, and collagen IV) in the glomeruli, typical of mesangial fibrosis, at >10 months of age
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• extensive tubulointerstitial fibrosis at 10 months of age
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small kidney
(
J:278754
)
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• kidneys appear smaller than normal upon necropsy at 10 months of age
• treatment with 2,4-diHB rescues macroscopic appearance of kidneys
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• renal tubule atrophy at >10 months of age
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• proteinaceous casts in dilated tubules at >10 months of age
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renal cast
(
J:278754
)
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• occasional protein casts in proximal tubules at 5 months of age
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pale kidney
(
J:278754
)
|
• kidneys appear pale upon necropsy at 10 months of age
• treatment with 2,4-diHB rescues macroscopic appearance of kidneys
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homeostasis/metabolism
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• males are more susceptible to proteinuria than females
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albuminuria
(
J:278754
)
|
• 7.4-fold increase in the albumin-to-creatinine ratio at 5 months of age
• up to 46.9-fold increase in albuminuria at 10 months of age
• treatment with 2,4-diHB protects mice from developing proteinuria
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cellular
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• increased number of mitochondria in podocytes at >10 months of age
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• enlarged mitochondria in podocytes at >10 months of age
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• increased size and number of mitochondria in podocytes at >10 months of age, indicating impaired mitochondrial function
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cardiovascular system
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• obliteration of glomerular capillary lumens at 10 months of age
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