Phenotypes associated with this allele

• Allele Symbol: Tg(Ins-Igf2)1Fbos
• Allele Name: transgene insertion 1, Fatima Bosch
• Allele ID: MGI:3818739
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Apob^tm2Sgy/Apob^tm2Sgy Ldlr^tm1Her/Ldlr^tm1Her Tg(Ins-Igf2)1Fbos/?	involves: 129S7/SvEvBrd * C57BL/6 * C57BL/6J * SJL	MGI:5771865
cx2	Apob^tm2Sgy/Apob^tm2Sgy Ldlr^tm1Her/Ldlr^tm1Her Tg(Ins-Igf2)1Fbos/?	involves: 129S7/SvEvBrd * C57BL/6 * SJL	MGI:4367111
tg3	Tg(Ins-Igf2)1Fbos/0	involves: C57BL/6 * C57BLKs/J * SJL	MGI:3818741
tg4	Tg(Ins-Igf2)1Fbos/0	involves: C57BL/6 * SJL	MGI:3818740

Genotype
MGI:5771865

cx1

• Allelic Composition: Apob^tm2Sgy/Apob^tm2Sgy; Ldlr^tm1Her/Ldlr^tm1Her; Tg(Ins-Igf2)1Fbos/?
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * C57BL/6J * SJL

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

homeostasis/metabolism

abnormal fasting circulating glucose level ( J:227165 )

♂ • fasting glycemia is increased on a standard chow diet

♂ • mice develop diabetes mellitus based on fasting hyperglycemia and lack of compensatory increase in insulin secretion when fed a high-fat/sucrose/cholesterol (HFSC) diet for 6 months

increased circulating insulin level ( J:227165 )

♂ • increase in fasting insulin levels on standard chow diet

increased circulating cholesterol level ( J:227165 )

♂ • mice exhibit cholesterolemia on both a standard chow diet and a high-fat/sucrose/cholesterol (HFSC) diet

cardiovascular system

abnormal aorta bulb morphology ( J:227165 )

♂ • mice fed the HFSC diet show higher expression of osteogenic genes in the aortic root

♂ • mice fed the HFSC diet show aortic root fibrosis

cardiac hypertrophy ( J:227165 )

♂ • HFSC-fed mice exhibit increased expression of hypertrophic cardiac markers

abnormal heart left ventricle morphology ( J:227165 )

♂ • increase in left ventricular mass on both a chow and HFSC diet

heart left ventricle hypertrophy ( J:227165 )

♂ • left ventricular hypertrophy in HFSC-fed mice

abnormal aortic valve morphology ( J:227165 )

♂ • mice fed the HFSC diet show aortic valve fibrosis

aortic valve stenosis ( J:227165 )

♂ • 80% of mice fed the HFSC diet for 6 months develop aortic stenosis, with mice showing increased peak aortic jet velocity, peak transvalvular pressure gradient, and mean transvalvular pressure gradient; magnitude of aortic stenosis is greater than in double Apob and Ldlr homozygotes

calcified aortic valve ( J:227165 )

♂ • HFSC-fed mice exhibit aortic valve calcification

small aortic valve ( J:227165 )

• aortic valve area is decreased in HFSC-fed mice

abnormal heart ventricles weight ( J:227165 )

♂ • total ventricular weight corrected for body weight is elevated in mice fed the HFSC diet

♂ • when corrected for tibia length, the total ventricular weight is increased in mice either on the chow or HFSC diet

cardiac fibrosis ( J:227165 )

♂ • mice fed the HFSC diet show aortic root fibrosis and aortic valve fibrosis

abnormal cardiovascular system physiology ( J:227165 )

♂ • echocardiography shows impaired left ventricular function in mice fed a chow diet with worsening cardiac dysfunction on the HFSC diet

♂ • the mitral E/E ratio (mitral inflow measured by pulsed-wave over tissue Doppler) is increased in mice on the HFSC diet

♂ • isovolumic relaxation time, corrected for heart rate, is decreased in mice on the HFSC diet

increased cardiac output ( J:227165 )

♂ • cardiac output is increased in mice fed the HFSC diet

increased cardiac stroke volume ( J:227165 )

♂ • stroke volume is increased in mice fed the HFSC diet

decreased cardiac muscle contractility ( J:227165 )

♂ • reduction in systolic fractional shortening in mice fed the HFSC diet

aortitis ( J:227165 )

♂ • some areas of the aortic surface leaflet from HFSC-fed mice are denuded of endothelial cells and show presence of inflammatory cell aggregates, platelets, and fibrin covering the extracellular matrix

immune system

aortitis ( J:227165 )

♂ • some areas of the aortic surface leaflet from HFSC-fed mice are denuded of endothelial cells and show presence of inflammatory cell aggregates, platelets, and fibrin covering the extracellular matrix

muscle

heart left ventricle hypertrophy ( J:227165 )

♂ • left ventricular hypertrophy in HFSC-fed mice

decreased cardiac muscle contractility ( J:227165 )

♂ • reduction in systolic fractional shortening in mice fed the HFSC diet

growth/size/body

cardiac hypertrophy ( J:227165 )

♂ • HFSC-fed mice exhibit increased expression of hypertrophic cardiac markers

heart left ventricle hypertrophy ( J:227165 )

♂ • left ventricular hypertrophy in HFSC-fed mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
aortic valve disease		DOID:62		J:227165
type 1 diabetes mellitus 2		DOID:0110741	OMIM:125852	J:227165

Genotype
MGI:4367111

cx2

• Allelic Composition: Apob^tm2Sgy/Apob^tm2Sgy; Ldlr^tm1Her/Ldlr^tm1Her; Tg(Ins-Igf2)1Fbos/?
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * SJL

homeostasis/metabolism

increased circulating glucose level ( J:141333 )

• elevated relative to mice lacking the transgene at 6 months regardless of diet

• difference from controls lacking the transgene persists on a high fat diet but not on a normal diet at 15 months

increased circulating insulin level ( J:141333 )

• plasma insulin levels are 2X control levels at 6 months in fed mice and fasted mice on a high fat diet

• fasted mice on a normal diet do not show elevated insulin

• reduced insulin sensitivity over the course of an insulin tolerance test

impaired glucose tolerance ( J:141333 )

• sustained elevation of blood glucose during a glucose tolerance test regardless of diet

• blood insulin is unchanged over the course of a glucose tolerance test

cardiovascular system

atherosclerotic lesions ( J:141333 )

• lesion thickness increases more on a high fat diet than does lesion area

• increased calcification of lesions after 15 months on a high fat diet, particularly for females

Genotype
MGI:3818741

tg3

• Allelic Composition: Tg(Ins-Igf2)1Fbos/0
• Genetic Background: involves: C57BL/6 * C57BLKs/J * SJL

homeostasis/metabolism

hyperglycemia ( J:141527 )

increased circulating insulin level ( J:141527 )

increased circulating free fatty acids level ( J:141527 )

• slight

increased circulating triglyceride level ( J:141527 )

• slight

insulin resistance ( J:141527 )

• Background Sensitivity: mice exhibit insulin resistance that is more severe than on a C57BL/6 SJL mixed background

endocrine/exocrine glands

pancreatic islet hyperplasia ( J:141527 )

• islet cells are larger, more elongated and more irregularly shared than in wild-type mice

disorganized pancreatic islets ( J:141527 )

• glucagon-producing cells are scattered throughout the islet core unlike in wild-type mice

growth/size/body

obese ( J:141527 )

• at 12 months of age, mice exhibit a 60% increase in body weight compared to a 27% increased in wild-type mice

liver/biliary system

hepatic steatosis ( J:141527 )

• at 12 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus 2		DOID:0110741	OMIM:125852	J:141527

Genotype
MGI:3818740

tg4

• Allelic Composition: Tg(Ins-Igf2)1Fbos/0
• Genetic Background: involves: C57BL/6 * SJL

endocrine/exocrine glands

increased pancreatic beta cell mass ( J:141527 )

• beta cell mass is increased 3-fold compared to in wild-type mice

pancreatic islet hyperplasia ( J:141527 )

• islet cells are larger, more elongated and more irregularly shared than in wild-type mice

disorganized pancreatic islets ( J:141527 )

• several core islet cells do not stain positive for insulin and glucagon-producing cells are scattered throughout the islet core unlike in wild-type mice

increased pancreas weight ( J:141527 )

• at 4 months of age, pancreatic weight is increased compared to in wild-type mice

abnormal pancreatic beta cell physiology ( J:141527 )

• when exposed to glucose, beta cells produce more insulin and exhibit increased glucose metabolism compared to in wild-type cells

increased insulin secretion ( J:141527 )

• at 4 months of age, beta cells secrete more insulin than wild-type cells when exposed to glucose

• insulin concentration in beta cells is 70% higher than in wild-type cells while pro-insulin levels are 6-fold higher than in wild-type cells

• when fed a high fat diet, mice exhibit increased compared to in similarly treated wild-type mice

homeostasis/metabolism

increased insulin secretion ( J:141527 )

• at 4 months of age, beta cells secrete more insulin than wild-type cells when exposed to glucose

• insulin concentration in beta cells is 70% higher than in wild-type cells while pro-insulin levels are 6-fold higher than in wild-type cells

• when fed a high fat diet, mice exhibit increased compared to in similarly treated wild-type mice

increased circulating glucose level ( J:141527 )

• at 3 months of age

hyperglycemia ( J:141527 )

• when fed a high fat diet, 30% of mice develop severe hyperglycemia and the remaining mice develop mild hyperglycemia compared to similarly treated wild-type mice

increased circulating insulin level ( J:141527 )

• at 1 month of age, insulin plasma levels are 3-fold higher than in wild-type mice

increased circulating free fatty acids level ( J:141527 )

• slight

increased circulating triglyceride level ( J:141527 )

• slight

insulin resistance ( J:141527 )

• at 4 months of age, mice exhibit insulin resistance

• Background Sensitivity: mice exhibit insulin resistance that is less severe than on a C57BL/6 C57BL/6Ks SJL mixed background

growth/size/body

increased pancreas weight ( J:141527 )

• at 4 months of age, pancreatic weight is increased compared to in wild-type mice

decreased susceptibility to weight gain ( J:141527 )

• when fed a high fat diet, 30% of mice lose 25% of their body weight unlike wild-type mice

• however, most mice exhibit a similar weight gain as observed in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus 2		DOID:0110741	OMIM:125852	J:141527