Phenotypes associated with this allele

• Allele Symbol: Tg(Ins2-Nos2)40Okam
• Allele Name: transgene insertion 40, Hiroshi Okamoto
• Allele ID: MGI:3706439
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Ager^tm1.1Hyam/Ager^+ Tg(Ins2-Nos2)40Okam/0	involves: 129P2/OlaHsd * C57BL/6 * CD-1 * DBA/2	MGI:3706543
cx2	Ager^tm1.1Hyam/Ager^tm1.1Hyam Tg(Ins2-Nos2)40Okam/0	involves: 129P2/OlaHsd * C57BL/6 * CD-1 * DBA/2	MGI:3706544
cx3	Tg(Ins2-Nos2)40Okam/0 Tg(Kdr-AGER)102Hyam/0	involves: C57BL/6J * CBA/J * CD-1 * DBA/2	MGI:3706554
tg4	Tg(Ins2-Nos2)40Okam/0	involves: 129P2/OlaHsd * C57BL/6 * CD-1 * DBA/2	MGI:3706545
tg5	Tg(Ins2-Nos2)40Okam/0	involves: C57BL/6 * CD-1 * DBA/2	MGI:3706514

Genotype
MGI:3706543

cx1

• Allelic Composition: Ager^tm1.1Hyam/Ager⁺; Tg(Ins2-Nos2)40Okam/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CD-1 * DBA/2

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

homeostasis/metabolism

hyperglycemia ( J:116040 )

• mice show sustained hyperglycemia (and display diabetes)

renal/urinary system

abnormal renal glomerulus morphology ( J:116040 )

• glomerular cell number is decreased compared to Ager-sufficient transgenic controls at 4 and 8 months

glomerulosclerosis ( J:116040 )

• progression of sclerosis is intermediate to Ager-sufficient or Ager-null transgenic mice

Genotype
MGI:3706544

cx2

• Allelic Composition: Ager^tm1.1Hyam/Ager^tm1.1Hyam; Tg(Ins2-Nos2)40Okam/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CD-1 * DBA/2

homeostasis/metabolism

decreased circulating creatinine level ( J:116040 )

• serum creatinine is much lower than in Ager-sufficient transgenic mice at 8 months

hyperglycemia ( J:116040 )

• mice show sustained hyperglycemia (and display diabetes)

albuminuria ( J:116040 )

• urinary albumin/creatinine ratio is much lower than in wild-type transgenic mice or nontransgenic controls at 4 and 8 months

renal/urinary system

albuminuria ( J:116040 )

• urinary albumin/creatinine ratio is much lower than in wild-type transgenic mice or nontransgenic controls at 4 and 8 months

abnormal renal glomerulus morphology ( J:116040 )

glomerulosclerosis ( J:116040 )

• progression of sclerosis is attenuated in mice compared to Ager-sufficient transgenic mice

abnormal kidney size ( J:116040 )

• kidney weight as percentage of body weight is attenuated with Ager-deficiency; kidney weight as percentage of body weight is lower than in wild-type transgenic mice but percentage is still higher than non-transgenic (non-diabetic) mice at 4 and 8 months

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:116040

Genotype
MGI:3706554

cx3

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

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

Genotype
MGI:3706545

tg4

• Allelic Composition: Tg(Ins2-Nos2)40Okam/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CD-1 * DBA/2

homeostasis/metabolism

increased circulating creatinine level ( J:116040 )

• serum creatinine is much higher than in Ager-deficient transgenic mice at 8 months

hyperglycemia ( J:116040 )

• mice show sustained hyperglycemia (and display diabetes)

albuminuria ( J:116040 )

• mice have much higher urinary albumin/creatinine ratio than Ager-deficient transgenic mice or nontransgenic mice at 4 and 8 months

renal/urinary system

albuminuria ( J:116040 )

• mice have much higher urinary albumin/creatinine ratio than Ager-deficient transgenic mice or nontransgenic mice at 4 and 8 months

abnormal kidney morphology ( J:116040 )

• compared to Ager-null transgenic mice, kidneys show changes associated with diabetic nephropathy such as increased S100 protein levels and AGE deposits

increased kidney weight ( J:116040 )

• kidney weight composes a higher percentage of body weight compared to transgenic mice at 4 and 8 months

abnormal renal glomerulus morphology ( J:116040 )

• accumulation of advanced glycation end product (AGE) deposits in renal glomeruli is greater than in Ager-deficient transgenics

growth/size/body

increased kidney weight ( J:116040 )

• kidney weight composes a higher percentage of body weight compared to transgenic mice at 4 and 8 months

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:116040

Genotype
MGI:3706514

tg5

• Allelic Composition: Tg(Ins2-Nos2)40Okam/0
• Genetic Background: involves: C57BL/6 * CD-1 * DBA/2

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:45520 )

• transgenic islet cells show extensive DNA strand breaks compared to control islets

decreased pancreatic beta cell mass ( J:45520 )

• proportion of insulin-producing cell mass to total pancreatic cell mass is markedly reduced at 4 weeks of age

• however, no infiltration of macrophages or lymphocytes (insulitis) is observed

homeostasis/metabolism

hyperglycemia ( J:45520 )

• mice show hyperglycemia by one week of age with blood glucose above 400 mg/dl

decreased circulating insulin level ( J:45520 )

• serum insulin level (0.53 ng/dl) is decreased compared to controls (3.68 ng/ml)

increased circulating ketone body level ( J:45520 )

• urine often tested positive for ketones

abnormal nitric oxide homeostasis ( J:45520 )

• nitrite levels in medium, indicative of NO release, increase in a time-dependent manner

• treatment with aminoguanidine (inhibitor of Nos2) delays elevation of blood glucose levels and reduction in pancreatic insulin contents; reduction in insulin producing cell mass is reduced or improved with treatment

increased urine glucose level ( J:45520 )

• urine glucose levels are 200-500 mg/dl by 1 week of age

renal/urinary system

increased urine glucose level ( J:45520 )

• urine glucose levels are 200-500 mg/dl by 1 week of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:4552