Phenotypes Associated with This Genotype

Genotype
MGI:3706554

• Allelic Composition: Tg(Ins2-Nos2)40Okam/0; Tg(Kdr-AGER)102Hyam/0
• Genetic Background: involves: C57BL/6J * CBA/J * CD-1 * DBA/2

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

homeostasis/metabolism

increased circulating creatinine level ( J:70495 )

• serum creatinine levels increase to 1.24 mg/dl

• treatment with an inhibitor of AGE formation improves serum creatinine levels at 6 months

hyperglycemia ( J:70495 )

• mice show hyperglycemia (and elevated serum HbA1c) by 2 months of age, indicative of a diabetic condition

albuminuria ( J:70495 )

• serum albumin/creatinine ratio becomes significantly higher at 4 months

renal/urinary system

increased kidney cell proliferation ( J:70495 )

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

increased kidney weight ( J:70495 )

• kidney weight to body weight ratios in double transgenic mice are increased compared to Tg(Ins2-Nos2)40Okam single transgenic mice

albuminuria ( J:70495 )

• serum albumin/creatinine ratio becomes significantly higher at 4 months

abnormal nephron morphology ( J:70495 )

• 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

expanded mesangial matrix ( J:70495 )

• 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

glomerulosclerosis ( J:70495 )

renal glomerulus hypertrophy ( J:70495 )

• 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

arteriosclerosis ( J:70495 )

• nodular lesions are observed in kidneys at 8 months of age

• treatment with an inhibitor of AGE formation improves sclerosis index at 6 months

atherosclerotic lesions ( J:70495 )

• nodular lesions are observed in kidneys at 8 months of age

cellular

increased kidney cell proliferation ( J:70495 )

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

growth/size/body

increased kidney weight ( J:70495 )

• kidney weight to body weight ratios in double transgenic mice are increased compared to Tg(Ins2-Nos2)40Okam single transgenic mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:70495