Analysis Tools
mortality/aging
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• ~50% of homozygotes are able to survive until 2 months of age
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• notable increase in mortality after the first week of life
• mutant mice that survived past two weeks failed to thrive, as evidenced by a lack of weight gain
• most die within the first month
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growth/size/body
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• homozygotes surviving to 2 months of age remain runted
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• weight of surviving mice reaches a plateau at ~2 weeks of age
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renal/urinary system
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• >50-fold increase in urinary excretion ratios of hypoxanthine to creatinine at 4 weeks of age
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• >50-fold increase in urinary excretion ratios of xanthine to creatinine at 4 weeks of age
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crystalluria
(
J:166326
)
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• presence of 50- to 100-um crystals in urinary samples
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• positive staining for osteopontin detected in renal epithelial cells at 4 weeks of age
• F4/80-positive macrophages invading the interstitial spaces between the renal tubules at 4 weeks of age
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• severe cystic dysplasia at 20 days of age
(J:103558)
• kidneys exhibit many yellow deposits containing lipids, as shown by Oil Red O staining
(J:166326)
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• glomeruli tend to be hypoplastic and primordial in appearance in immature and dysplastic areas
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• abnormal postnatal kidney development, as shown by presence of immature parenchyma
• multifocal immature areas that often coalesce to encompass the entire kidney
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• significant interstitial fibrosis detected around the dilated renal tubules at 4 weeks of age, as shown by Masson trichrome staining
• positive staining for TGF-beta and connective tissue growth factor (CTGF), both key regulators of fibrosis, detected in the cytosol and the nucleus of renal tubular cells, respectively, at 4 weeks of age
• positive staining for alpha-smooth muscle actin (alpha-SMA, a marker of epithelial-mesenchymal transition) detected in both tubuloepithelial and interstitial cells at 4 weeks of age
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small kidney
(
J:103558
)
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• accumulation of triglyceride-rich deposits and insoluble crystals in the renal tubules at 4 weeks of age, unlike in wild-type controls
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• in culture, primary renal epithelial cells display a change in morphology from a cuboidal to a fibroblastic shape
• transformation of primary renal epithelial cells to myofibroblasts is accompanied by increased expression of TGF-beta, vimentin, and alpha-SMA (a marker of epithelial-mesenchymal transition)
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• ectatic to cystic tubules at 20 days of age
(J:103558)
• at 4 weeks of age
(J:166326)
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• pale yellow kidneys at 4 weeks of age
(J:166326)
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• homozygotes die of renal failure
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homeostasis/metabolism
| N |
• normal serum creatinine levels relative to wild-type and heterozygous mice
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• nearly three times higher blood urea nitrogen (BUN) levels than wild-type
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• levels of serum uric acid below detection
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• significantly increased blood concentrations of hypoxanthine at 4 weeks of age, unlike in wild-type controls
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• mildly elevated serum amylase levels, presumably due to decreased renal clearance
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• significantly increased blood concentrations of xanthine at 4 weeks of age, unlike in wild-type controls
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• pimonidazole-positive cells, indicating tissue hypoxia, detected in the segmental region of kidney proximal tubular cells at 4 weeks of age
• hypoxia-inducible factor 1alpha-positive staining detected in the nucleus of kidney proximal tubular cells at 4 weeks of age
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• expression of adipogenesis-related genes is significantly elevated in the kidney at 4 weeks of age
• however, the level of lipogenesis-related gene expression is comparable to that in wild-type kidneys
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• significantly elevated ratio of triglyceride to phospholipid levels in kidney at 4 weeks of age
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• >50-fold increase in urinary excretion ratios of hypoxanthine to creatinine at 4 weeks of age
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• >50-fold increase in urinary excretion ratios of xanthine to creatinine at 4 weeks of age
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crystalluria
(
J:166326
)
|
• presence of 50- to 100-um crystals in urinary samples
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immune system
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• positive staining for osteopontin detected in renal epithelial cells at 4 weeks of age
• F4/80-positive macrophages invading the interstitial spaces between the renal tubules at 4 weeks of age
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cellular
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• increased 4-HNE-positive staining in interstitial cells and 8-oxo-7,8-dihydro-2'-deoxyguanosine-positive staining in the nucleus of kidney interstitial and epithelial cells at 4 weeks of age
• significant accumulation of nitrotyrosine and malondialdehyde at 4 and 8 weeks of age
• however, normal amounts of oxidative products are detected until 2 weeks of age
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adipose tissue
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• reduced visceral fat content at 4 weeks of age
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