Mouse Genome Informatics
cx
    Tg(Ins2-Nos2)40Okam/0
Tg(Kdr-AGER)102Hyam/0

involves: C57BL/6J * CBA/J * CD-1 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
homeostasis/metabolism
• serum creatinine levels increase to 1.24 mg/dl
• treatment with an inhibitor of AGE formation improves serum creatinine levels at 6 months
• mice show hyperglycemia (and elevated serum HbA1c) by 2 months of age, indicative of a diabetic condition
• serum albumin/creatinine ratio becomes significantly higher at 4 months

renal/urinary system
• glomerular cell proliferation is accelerated in double transgenics compared to controls
• serum albumin/creatinine ratio becomes significantly higher at 4 months
• kidney weight to body weight ratios in double transgenic mice are increased compared to Tg(Ins2-Nos2)40Okam single transgenic mice
• treatment with an inhibitor of advanced glycation end product (AGE) formation suppresses diabetic nephropathy; AGE levels in blood in double transgenic and single transgenic diabetic controls are reduced ~to levels in nondiabetic animals
• Tg(Ins2-Nos2)40Okam single transgenic controls and double transgenic kidneys display mesangial expansion compared to controls; at 4 months, severity is greater in double transgenic mice with ~50 glomeruli/mouse showing increases in mesangium area, mesangium fraction, and sclerosis index
• lesions observed double transgenic or Tg(Ins2-Nos2)40Okam single transgenic controls include glomerular cell proliferation and glomerular hypertrophy; these pathological features are accelerated in double transgenics compared to controls

cardiovascular system
• nodular lesions are observed in kidneys at 8 months of age
• treatment with an inhibitor of AGE formation improves sclerosis index at 6 months
• nodular lesions are observed in kidneys at 8 months of age

cellular
• glomerular cell proliferation is accelerated in double transgenics compared to controls

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Insulin-Dependent; IDDM 222100 J:70495