mortality/aging
• approximate 40% survival up to 62 weeks
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• about 40% of mice die within 5 weeks after birth
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homeostasis/metabolism
• insulin secretion from islets in males is decreased by 20.56% at an elevated glucose concentration
• 8-week old males secrete lower amount of insulin at 15 and 30 minutes after a glucose injection
• males treated with allopurinol show improved islet function
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• serum creatinine is elevated
• males treated with allopurinol show reduced serum creatinine levels
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• blood urea nitrogen is elevated
• males treated with allopurinol show reduced BUN levels
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• mice exhibit higher serum uric acid levels
• males have higher serum uric acid levels that females
• male mice treated with urate-lowering drugs allopurinol, benzbromarone, or febuxostat show reduced serum uric acid levels
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• total cholesterol is elevated in females
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• low-density lipoprotein cholesterol levels are elevated in females
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• triglyceride levels are decreased in males
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• triglyceride levels are elevated in females
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• upon glucose tolerance test, blood glucose at 15 and 30 minutes after initiation is higher in males than in control males
• however, neither fasting insulin or fasting glucose are changed and no lesions are seen in pancreatic islets and mice do not exhibit insulin resistance in the insulin tolerance test
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• mRNA expression of inflammatory cytokines F4/80 and interlukin-1beta are elevated in the kidneys
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• 87.5% of males and 80% of females develop diabetes at day 20 after streptozotocin (STZ) treatment, at higher rates than in wild-type mice
• onset of STZ-induced diabetes occurs earlier in males than females
• pancreas from STZ-treated males show many atrophic islets associated with reduced number of insulin-positive beta cells
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renal/urinary system
• severe nonspecific chronic corticomedullar inflammation is seen in the kidney, with mice showing substantial lymphocyte (CD3+) and macrophage (CD68+) infiltration
• males treated with allopurinol show alleviation of lymphocyte and macrophage infiltration in the kidney
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• lesions in kidney tissues are seen at 6 weeks of age
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• urate crystals are seen in kidney interstices
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• kidneys show focal tubulointerstitial fibrosis at 8 weeks of age
• however, treatment with allopurinol does not change the tubulointerstitial fibrosis
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• kidneys show collapsed and necrotic nephrons at 8 weeks of age
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• 8-week old mice show dilated Bowmans spaces
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• 8-week old mice show dilated tubules
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• kidneys show necrotic nephrons at 8 weeks of age
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cardiovascular system
• 8-week old females, but not males, develop higher systolic and diastolic blood pressure than controls
• females treated with allopurinol show decreased systolic and diastolic blood pressure levels to normal levels
• however, neither cardiac dimensional (mass, volume, inner diameter, or wall thickness of the left ventricle) nor functional parameters (cardiac output, stroke volume, fractional shorting, and ejection fraction) are altered
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endocrine/exocrine glands
• STZ-treated males show increased beta-cell apoptosis compared to wild-type males
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• beta-cell mass of STZ-treated males is lower than that of wild-type males
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• insulin secretion from islets in males is decreased by 20.56% at an elevated glucose concentration
• 8-week old males secrete lower amount of insulin at 15 and 30 minutes after a glucose injection
• males treated with allopurinol show improved islet function
|
immune system
• mRNA expression of inflammatory cytokines F4/80 and interlukin-1beta are elevated in the kidneys
|
• severe nonspecific chronic corticomedullar inflammation is seen in the kidney, with mice showing substantial lymphocyte (CD3+) and macrophage (CD68+) infiltration
• males treated with allopurinol show alleviation of lymphocyte and macrophage infiltration in the kidney
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cellular
• STZ-treated males show increased beta-cell apoptosis compared to wild-type males
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
hyperuricemia | DOID:1920 | J:271949 |