Analysis Tools
mortality/aging
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• all surviving mice die between 3 and 8 weeks of age, with an average life span of 28.4 days
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• pups are reported to show high perinatal lethality; however, the exact frequency could not be determined due to cannibalization by the mother
• only a few mice are recovered at weaning, with an increased frequency of dead pups noted after birth
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growth/size/body
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• at 4 weeks of age, mice are overtly smaller than wild-type controls (runted)
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• at 4 weeks of age, body weight is about half that of wild-type controls
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• mice stop gaining weight after the first 2 weeks of life
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renal/urinary system
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• ApopTag staining showed increased apoptosis of renal tubule epithelial cells at 4 weeks of age
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• immunofluorescence staining of Ki67 showed markedly increased kidney cell proliferation at 4 weeks of age
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• mice exhibit a transparent urine, unlike in control littermates where urine has a yellow color
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• at 4 weeks of age, urine hypoxanthine levels are significantly higher than those in age-matched controls
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• at 4 weeks of age, the urine pH is significantly lower i.e., more acidic than that in control littermates
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• at 4 weeks of age, urine xanthine levels are significantly higher than those in age-matched controls
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• obstructive nephropathy is associated with moderate interstitial inflammatory responses
• genes involved in the inflammatory response (Tnf, Ccl2) are significantly upregulated in the kidneys at 4 weeks of age
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• the interstitial space is somewhat edematous and, adjacent to dilated collecting ducts, cortical areas show mononuclear cell infiltrates (mainly in the subcapsular area)
• some dilated tubules are filled with PMNs
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• at 4 weeks of age, kidneys exhibit an irregular outer contour due to numerous scars and cystoid tubules
• mice develop intra- and extrarenal obstructive nephropathy due to accumulation of xanthine crystals
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• round lamellate deposits of Tamm-Horsfall (uromodulin) protein (THP) are present in the dilated and nondilated collecting ducts
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• in areas of tubular atrophy, glomeruli lay close together, are variable in size and show collapsed capillary loops but are very rarely sclerotic
• no primary lesions in glomeruli and vessels are detected
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• in areas of tubular atrophy, glomeruli have collapsed capillary loops
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• tubular epithelium is flattened or necrotic with intraluminal cell debris containing neutrophils and a few multinucleated giant cells surrounding the THP deposits
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• adjacent to dilated collecting ducts, cortical areas show interstitial fibrosis
• genes involved in interstitial fibrosis (Tgfb1 and Serpine1) are significantly upregulated in the kidneys at 4 weeks of age
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• Tamm-Horsfall (uromodulin) protein (THP) deposits are detected in the renal pelvis with damage of the urothelium, accompanied by inflammation in the surrounding tissue
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• damage of the urothelium with denudation of the pelvic smooth muscle wall is observed
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• some deposits of THP are found in the renal pelvis; these deposits are shown to adhere to the urothelium leading to urothelial damage and loss
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• mice that survive to 2 months of age exhibit occasional hydronephrosis
• in mice with unilateral ureteral obstruction, the affected kidney is enlarged with a uniformly thin, atrophic renal cortex and a marked dilation of the renal pelvis, typical of hydronephrosis
• in contrast, the contralateral kidney is small with obstructive nephropathy
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small kidney
(
J:336718
)
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• at 4 weeks of age, average kidney size is reduced by 50% as determined by planimetry
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• at 4 weeks of age, mice show decreased kidney weight with a 33% reduction in kidney/body weight ratio relative to control littermates
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• adjacent to dilated collecting ducts, cortical areas display tubular atrophy
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• renal tubules exhibit cystic dilation, mainly in the cortex and less in the medulla
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• tubular cell necrosis is observed
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renal cast
(
J:336718
)
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• intratubular deposits of round lamellate deposits of Tamm-Horsfall (uromodulin) protein (THP) with occasionally embedded crystals are observed
• such deposits often exhibit a basophilic rim suggestive of calcification but have negative von Kossa staining and no birefringent crystals are found after PFA fixation
• few empty crystal clefts are present
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• stones are frequently observed in the urine and kidneys; kidney stones are composed of xanthine based on Raman spectral fingerprints
• ~5% of mice exhibit stones in the pelvis, sometimes leading to ureteral obstruction
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pale kidney
(
J:336718
)
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• ~5% of mice exhibit stones in the pelvis, sometimes leading to ureteral obstruction; this obstruction is primarily unilateral, and kidneys have a pale and swollen appearance
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• mice die prematurely due to renal failure
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immune system
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• obstructive nephropathy is associated with moderate interstitial inflammatory responses
• genes involved in the inflammatory response (Tnf, Ccl2) are significantly upregulated in the kidneys at 4 weeks of age
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• the interstitial space is somewhat edematous and, adjacent to dilated collecting ducts, cortical areas show mononuclear cell infiltrates (mainly in the subcapsular area)
• some dilated tubules are filled with PMNs
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homeostasis/metabolism
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• at 4 weeks of age, serum creatinine level is drastically higher than that in age-matched controls
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• at 4 weeks of age, serum urea level is drastically higher than that in age-matched controls
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• at 4 weeks of age, the serum uric acid level is almost undetectable
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• at 4 weeks of age, serum hypoxanthine levels are significantly higher than those in age-matched controls
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• at 4 weeks of age, serum alanine aminotransferase level is significantly lower than that in age-matched controls
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• at 4 weeks of age, serum alkaline phosphatase level is significantly higher than that in age-matched controls
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• at 4 weeks of age, serum xanthine levels are significantly higher than those in age-matched controls
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• mice exhibit a transparent urine, unlike in control littermates where urine has a yellow color
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• at 4 weeks of age, urine hypoxanthine levels are significantly higher than those in age-matched controls
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• at 4 weeks of age, the urine pH is significantly lower i.e., more acidic than that in control littermates
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• at 4 weeks of age, urine xanthine levels are significantly higher than those in age-matched controls
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• mice show major alterations in the metabolism of purines, amino acids, and phospholipids in the kidney
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• mice show major alterations in the metabolism of amino acids in the kidney
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• mice show major alterations in the metabolism of phospholipids in the kidney
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cellular
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• ApopTag staining showed increased apoptosis of renal tubule epithelial cells at 4 weeks of age
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• immunofluorescence staining of Ki67 showed markedly increased kidney cell proliferation at 4 weeks of age
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• xanthinuric mice exhibit disrupted intrarenal redox homeostasis and impaired ability to overcome oxidative stress and inflammation in the kidney
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hematopoietic system
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• at 4 weeks of age, mice exhibit a mild anemia with decreased circulating red blood cells and red cell parameter values outside normal ranges
• values of mean corpuscular volume and mean corpuscular hemoglobin concentration are normal, suggestive of normocytic anemia
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• at 4 weeks of age, hematocrit in blood (%) is significantly lower than that in age-matched controls
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• at 4 weeks of age, hemoglobin in blood (g/dl) is significantly lower than that in age-matched controls
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liver/biliary system
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• at 4 weeks of age, mice show decreased liver weight with a 20% reduction in liver/body weight ratio relative to control littermates
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nervous system
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• at 4 weeks of age, mice show a 51% increase in brain/body weight ratio
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cardiovascular system
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• in areas of tubular atrophy, glomeruli have collapsed capillary loops
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adipose tissue
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• adipogenesis-related genes (Cebpb and Pparg) are significantly upregulated at 4 weeks of age
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behavior/neurological
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• pup cannibalization by the mother is observed
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| obstructive nephropathy | DOID:0070314 | J:336718 | ||
| xanthinuria type II | DOID:0070453 |
OMIM:603592 |
J:336718 | |
