All Phenotypes Uox<em1Cli> MGI Mouse

decreased survivor rate ( J:271949 )

• approximate 40% survival up to 62 weeks

premature death ( J:271949 )

• about 40% of mice die within 5 weeks after birth

decreased insulin secretion ( J:271949 )

• 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

increased circulating creatinine level ( J:271949 )

• serum creatinine is elevated

• males treated with allopurinol show reduced serum creatinine levels

increased blood urea nitrogen level ( J:271949 )

• blood urea nitrogen is elevated

• males treated with allopurinol show reduced BUN levels

increased blood uric acid level ( J:271949 )

• 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

increased circulating cholesterol level ( J:271949 )

• total cholesterol is elevated in females

increased circulating LDL cholesterol level ( J:271949 )

• low-density lipoprotein cholesterol levels are elevated in females

decreased circulating triglyceride level ( J:271949 )

• triglyceride levels are decreased in males

increased circulating triglyceride level ( J:271949 )

• triglyceride levels are elevated in females

impaired glucose tolerance ( J:271949 )

• 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

abnormal cytokine level ( J:271949 )

• mRNA expression of inflammatory cytokines F4/80 and interlukin-1beta are elevated in the kidneys

increased susceptibility to non-insulin-dependent diabetes ( J:271949 )

• 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

kidney inflammation ( J:271949 )

• 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

abnormal kidney morphology ( J:271949 )

• lesions in kidney tissues are seen at 6 weeks of age

abnormal kidney interstitium morphology ( J:271949 )

• urate crystals are seen in kidney interstices

renal interstitial fibrosis ( J:271949 )

• kidneys show focal tubulointerstitial fibrosis at 8 weeks of age

• however, treatment with allopurinol does not change the tubulointerstitial fibrosis

abnormal nephron morphology ( J:271949 )

• kidneys show collapsed and necrotic nephrons at 8 weeks of age

increased glomerular capsule space ( J:271949 )

• 8-week old mice show dilated Bowmans spaces

dilated renal tubule ( J:271949 )

• 8-week old mice show dilated tubules

nephron necrosis ( J:271949 )

• kidneys show necrotic nephrons at 8 weeks of age

increased systemic arterial blood pressure ( J:271949 )

• 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

increased pancreatic beta cell apoptosis ( J:271949 )

• STZ-treated males show increased beta-cell apoptosis compared to wild-type males

decreased pancreatic beta cell mass ( J:271949 )

• beta-cell mass of STZ-treated males is lower than that of wild-type males