All Phenotypes Insr<tm1Khn> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Insr^tm1Khn
targeted mutation 1, Ronald Kahn
MGI:2384332

Summary

19 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Insr^tm1Khn/Insr^tm1Khn Lepr^tm1.1Chua/Lepr^tm1.1Chua Tg(Pomc1-cre)16Lowl/0	involves: 129 * 129S4/SvJae * 129S6/SvEvTac * C57BL/6J * FVB/N	MGI:5471586
cn2	Insr^tm1Khn/Insr^tm1Khn Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺	involves: 129S4/SvJae * C57BL/6 * C57BL/6J	MGI:6791351
cn3	Insr^tm1Khn/Insr^tm1Khn Tg(Ins2-cre)25Mgn/0	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:3775383
cn4	Insr^tm1Khn/Insr^tm1Khn Pdx1^tm1Ted/Pdx1⁺ Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:3583116
cn5	Insr^tm1Khn/Insr^tm1Khn Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:3775385
cn6	Insr^tm1Khn/Insr^tm1Khn Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺ Tg(Ins2-cre)25Mgn/0	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:3775382
cn7	Insr^tm1Khn/Insr^tm1Khn Tg(Ckmm-cre)5Khn/0	involves: 129S4/SvJae * C57BL/6 * FVB	MGI:3775309
cn8	Insr^tm1Khn/Insr^tm1Khn Tg(Pdgfrb-cre)#Rha/0	involves: 129S4/SvJae * C57BL/6J	MGI:7327617
cn9	Insr^tm1Khn/Insr^tm1Khn Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺	involves: 129S4/SvJae * C57BL/6J * DBA/2 * FVB	MGI:3039262
cn10	Insr^tm1Khn/Insr^tm1Khn Tg(Ckmm-cre)5Khn/0	involves: 129S4/SvJae * C57BL/6J * FVB	MGI:2389585
cn11	Insr^tm1Khn/Insr^tm1Dac Tg(Ckmm-cre)5Khn/0	involves: 129S4/SvJae * C57BL/6J * FVB	MGI:2389586
cn12	Insr^tm1Khn/Insr^tm1Khn Tg(Nes-cre)1Kln/0	involves: 129S4/SvJae * C57BL/6J * SJL	MGI:3583775
cn13	Insr^tm1Khn/Insr^tm1Khn Tg(Nes-cre)1Kln/0	involves: 129S4/SvJae * C57BL/6 * SJL	MGI:3629045
cn14	Insr^tm1Khn/Insr^tm1Khn Tg(Myhca-cre)1Abel/0	involves: 129S4/SvJae * FVB	MGI:3620045
cn15	Insr^tm1Khn/Insr^tm1Khn Tg(Slc2a4-cre)546Dac/0	involves: 129S4/SvJaeSor * C57BL/6 * FVB	MGI:4941586
cn16	Igf1r^tm1.1Mhz/Igf1r⁺ Insr^tm1Khn/Insr^tm1Khn Tg(Ckmm-cre)5Khn/0	involves: 129/Sv * 129S4/SvJae * C57BL/6 * FVB	MGI:3775310
cn17	Igf1r^tm1.1Mhz/Igf1r^tm1.1Mhz Insr^tm1Khn/Insr^tm1Khn Tg(Ckmm-cre)5Khn/0	involves: 129/Sv * 129S4/SvJae * C57BL/6 * FVB	MGI:3775311
cn18	Igf1r^tm1.1Mhz/Igf1r^tm1.1Mhz Insr^tm1Khn/Insr⁺ Tg(Ckmm-cre)5Khn/0	involves: 129/Sv * 129S4/SvJae * C57BL/6 * FVB	MGI:3775313
cx19	Igf1r^tm1.1Mhz/Igf1r^tm1.1Mhz Insr^tm1Khn/Insr^tm1Khn	involves: 129/Sv * 129S4/SvJae * C57BL/6 * FVB	MGI:3775314

Allelic Composition	Insr^tm1Khn/Insr^tm1Khn Lepr^tm1.1Chua/Lepr^tm1.1Chua Tg(Pomc1-cre)16Lowl/0
Genetic Background	involves: 129 * 129S4/SvJae * 129S6/SvEvTac * C57BL/6J * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Insr^tm1Khn mutation (1 available); any Insr mutation (94 available)
Lepr^tm1.1Chua mutation (1 available); any Lepr mutation (121 available)
Tg(Pomc1-cre)16Lowl mutation (1 available)

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

adipose tissue

increased abdominal adipose tissue amount ( J:192274 )

• trend towards increased intra-abdominal adiposity at 4 months of age

increased fat cell size ( J:192274 )

• perigonadal adipocyte hypertrophy at 4 months of age

abnormal gonadal fat pad morphology ( J:192274 )

• perigonadal adipocyte hypertrophy at 4 months of age

• an increase in macrophage accumulation is seen in the perigonadal fat indicating inflammation

increased percent body fat/body weight ( J:192274 )

• percent body fat is increased in females at 4 months of age, however absolute body weight is not increased at this time

white adipose tissue inflammation ( J:192274 )

• an increase in macrophage accumulation is seen in the perigonadal fat, and macrophage marker analysis and cytokine expression indicates low-grade inflammation in adipose tissue

endocrine/exocrine glands

absent corpus luteum ( J:192274 )

• 45% of mice lack either corpora lutea or preovulatory follicles

absent mature ovarian follicles ( J:192274 )

• 45% of mice lack either corpora lutea or preovulatory follicles

ovary inflammation ( J:192274 )

• low-grade inflammation as indicated by increased IL-6 expression in the ovary

growth/size/body

decreased lean body mass ( J:192274 )

• percent lean body mass is decreased at 4 months of age

homeostasis/metabolism

hyperglycemia ( J:192274 )

• females are hyperglycemic before (at 3 months of age) and during pregnancy (at gestational days 12 and 15), without evidence of gestational glucose intolerance

increased circulating leptin level ( J:192274 )

• circulating levels of adipokine leptin are increased at 4 months of age

immune system

white adipose tissue inflammation ( J:192274 )

• an increase in macrophage accumulation is seen in the perigonadal fat, and macrophage marker analysis and cytokine expression indicates low-grade inflammation in adipose tissue

ovary inflammation ( J:192274 )

• low-grade inflammation as indicated by increased IL-6 expression in the ovary

liver inflammation ( J:192274 )

• low-grade inflammation as indicated by increased IL-1beta expression in the liver

liver/biliary system

liver inflammation ( J:192274 )

• low-grade inflammation as indicated by increased IL-1beta expression in the liver

reproductive system

absent corpus luteum ( J:192274 )

• 45% of mice lack either corpora lutea or preovulatory follicles

absent mature ovarian follicles ( J:192274 )

• 45% of mice lack either corpora lutea or preovulatory follicles

ovary inflammation ( J:192274 )

• low-grade inflammation as indicated by increased IL-6 expression in the ovary

decreased ovulation rate ( J:192274 )

• females exhibit reduced ovulation but show normal cycling suppression from fasting

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
polycystic ovary syndrome		DOID:11612	OMIM:184700	J:192274

Allelic Composition	Insr^tm1Khn/Insr^tm1Khn Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
Genetic Background	involves: 129S4/SvJae * C57BL/6 * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Insr^tm1Khn mutation (1 available); any Insr mutation (94 available)
Speer6-ps1^{Tg(Alb-cre)21Mgn} mutation (6 available); any Speer6-ps1 mutation (4 available)

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

homeostasis/metabolism

hyperglycemia ( J:234643 )

• at 2 months of age, mice show hyperglycemia in the fed state

• however, blood glucose levels become normal by 6 months of age

increased circulating insulin level ( J:234643 )

• at 2 months of age, mice show hyperinsulinemia in the fed state that is more severe than in Mad2l1bp^tm1.1Itl/Mad2l1bp^tm1.1Itl Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺ mice

impaired glucose tolerance ( J:234643 )

• at 2 months of age, mice show severe glucose intolerance

• surprisingly, glucose intolerance is not severe at 6 months of age

decreased liver glycogen level ( J:234643 )

• at 2 months of age, liver glycogen levels are decreased to a greater extent than in Mad2l1bp^tm1.1Itl/Mad2l1bp^tm1.1Itl Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺ mice

insulin resistance ( J:234643 )

• at 2 months of age, mice show severe insulin intolerance

• surprisingly, insulin intolerance is not severe at 6 months of age

abnormal enzyme/coenzyme activity ( J:234643 )

• insulin treatment fails to stimulate glycogen synthase activity in hepatocytes, unlike in wild-type hepatocytes

liver/biliary system

abnormal liver morphology ( J:234643 )

• at 2 months of age, males show scattered focal dysplasia in the periportal area of the liver

• however, overall liver architecture is normal

decreased liver glycogen level ( J:234643 )

• at 2 months of age, liver glycogen levels are decreased to a greater extent than in Mad2l1bp^tm1.1Itl/Mad2l1bp^tm1.1Itl Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺ mice

abnormal liver physiology ( J:234643 )

• insulin receptor (IR) autophosphorylation and activating phosphorylation of AKT (pT308) are significantly reduced whereas inhibitory phosphorylation of GSK3 (pS9) is modestly reduced in whole-liver lysates from insulin-treated mice

abnormal hepatocyte physiology ( J:234643 )

• insulin-dependent glycogen synthase (GS) activation is abolished in hepatocytes

Allelic Composition	Insr^tm1Khn/Insr^tm1Khn Tg(Ins2-cre)25Mgn/0
Genetic Background	involves: 129S4/SvJae * C57BL/6 * DBA/2

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Insr^tm1Khn mutation (1 available); any Insr mutation (94 available)
Tg(Ins2-cre)25Mgn mutation (2 available)

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

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:121640 )

• when fed a high fat diet, 30% of mice die by 16 weeks

premature death ( J:121640 )

• some mice die due to severe hyperglycemia

homeostasis/metabolism

decreased insulin secretion ( J:121640 )

hyperglycemia ( J:121640 )

• mice exhibit an increase in serum glucose level on a regular diet and a severe increase when fed a high fat diet

impaired glucose tolerance ( J:121640 )

• mice exhibit impaired glucose tolerance on a normal diet and severe intolerance when fed a high fat diet

• however, mice are not insulin resistant

endocrine/exocrine glands

decreased pancreatic beta cell mass ( J:121640 )

• mice exhibit decreased beta cell mass when fed a normal or high fat diet

decreased insulin secretion ( J:121640 )

Allelic Composition	Insr^tm1Khn/Insr^tm1Khn Pdx1^tm1Ted/Pdx1⁺ Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
Genetic Background	involves: 129S4/SvJae * C57BL/6 * DBA/2

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Insr^tm1Khn mutation (1 available); any Insr mutation (94 available)
Pdx1^tm1Ted mutation (0 available); any Pdx1 mutation (35 available)
Speer6-ps1^{Tg(Alb-cre)21Mgn} mutation (6 available); any Speer6-ps1 mutation (4 available)

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

endocrine/exocrine glands

decreased pancreatic beta cell mass ( J:92861 )

• these mutants fail to exhibit an adaptive islet hyperplastic response to insulin resistance; instead, pancreatic beta cell mass is reduced, and islets appear small with scattered non-beta cells

Allelic Composition	Insr^tm1Khn/Insr^tm1Khn Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
Genetic Background	involves: 129S4/SvJae * C57BL/6 * DBA/2

Find Mice

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

homeostasis/metabolism

decreased circulating glucose level ( J:121640 )

• at 10 to 12 months of age

hyperglycemia ( J:121640 )

• while mice display normoglycemia during the first 3 weeks of life, at 4 weeks mice develop hypoglycemia that lasts until week 6

increased circulating insulin level ( J:121640 )

impaired glucose tolerance ( J:121640 )

insulin resistance ( J:121640 )

endocrine/exocrine glands

increased pancreatic beta cell mass ( J:121640 )

• at 2 weeks beta cell mass is increased 2-fold and at 6 weeks 4-fold compared to in wild-type mice due to increased mitosis of beta cells

• at 10 to 12 months of age, mice exhibit a 27-fold increase in beta cell mass due to an 8-fold increase in proliferating beta cells with a slight increase in apoptosis

Allelic Composition	Insr^tm1Khn/Insr^tm1Khn Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺ Tg(Ins2-cre)25Mgn/0
Genetic Background	involves: 129S4/SvJae * C57BL/6 * DBA/2

Find Mice

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

mortality/aging

premature death ( J:121640 )

• 82% of mice die by 6 weeks of age with some mice surviving a few weeks longer

homeostasis/metabolism

decreased insulin secretion ( J:121640 )

hyperglycemia ( J:121640 )

• mice develop hypoglycemia at 2 weeks of age that rapidly worsens by 6 weeks of age

• mice exhibit high fasting glucose serum levels

increased circulating insulin level ( J:121640 )

impaired glucose tolerance ( J:121640 )

insulin resistance ( J:121640 )

endocrine/exocrine glands

decreased insulin secretion ( J:121640 )

renal/urinary system

polyuria ( J:121640 )

• during terminal stages

behavior/neurological

polydipsia ( J:121640 )

• during terminal stages

digestive/alimentary system

digestive/alimentary phenotype ( J:121640 )

N	• unlike mice null for Insr in beta cells mice, islet cell mass is not increased despite similar levels of elevated insulin levels

growth/size/body

decreased body weight ( J:121640 )

• mice develop severe diabetes and loss 30% of their body weight in terminal stages

Allelic Composition	Insr^tm1Khn/Insr^tm1Khn Tg(Ckmm-cre)5Khn/0
Genetic Background	involves: 129S4/SvJae * C57BL/6 * FVB

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Insr^tm1Khn mutation (1 available); any Insr mutation (94 available)
Tg(Ckmm-cre)5Khn mutation (4 available)

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

cardiovascular system

cardiovascular system phenotype ( J:118987 )

N	• heart function and morphology is normal

growth/size/body

growth/size/body region phenotype ( J:118987 )

N	• mice exhibit normal growth rates

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:118987 )

N	• mice exhibit normal glucose homeostasis

Allelic Composition	Insr^tm1Khn/Insr^tm1Khn Tg(Pdgfrb-cre)#Rha/0
Genetic Background	involves: 129S4/SvJae * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Insr^tm1Khn mutation (1 available); any Insr mutation (94 available)
Tg(Pdgfrb-cre)#Rha mutation (0 available)

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

vision/eye

abnormal retina vasculature morphology ( J:327000 )

• mice show increased vascularity in the regions adjacent to retinal veins

• the number of sprouting tip cells is increased indicating increased angiogenic sporouting in superficial and deep layers

• however, pericyte coverage of capillaries is unaltered in perivenous and periartieral plexi and no differences in vascular regression or endothelial proliferation is seen

abnormal retina blood vessel morphology ( J:327000 )

• mice show increased retinal vein diameter at P5 and P10

abnormal retina blood vessel pattern ( J:327000 )

• mice show impaired venous pattering during developmental retinal angiogenesis with increased branching complexity in the peripheral half of the plexus at P5

cardiovascular system

abnormal retina vasculature morphology ( J:327000 )

• mice show increased vascularity in the regions adjacent to retinal veins

• the number of sprouting tip cells is increased indicating increased angiogenic sporouting in superficial and deep layers

• however, pericyte coverage of capillaries is unaltered in perivenous and periartieral plexi and no differences in vascular regression or endothelial proliferation is seen

abnormal retina blood vessel morphology ( J:327000 )

• mice show increased retinal vein diameter at P5 and P10

abnormal retina blood vessel pattern ( J:327000 )

• mice show impaired venous pattering during developmental retinal angiogenesis with increased branching complexity in the peripheral half of the plexus at P5

abnormal vascular plexus formation ( J:327000 )

• mice exhibit abnormal retinal venous plexus development in early postnatal life, with increased branching complexity in the peripheral half of the plexus, increased venous plexus vascular density but not arterial plexus density, and increased vascular area of the deep vascular plexus indicating venous plexus hypervascularity

• perivenous hypervascularity diminishes with time, although it is still evident at P10

homeostasis/metabolism

increased circulating insulin level ( J:327000 )

• fasting serum insulin is increased in 8-week-old mice

• however, fasting serum glucose is normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
diabetic retinopathy		DOID:8947		J:327000

Allelic Composition	Insr^tm1Khn/Insr^tm1Khn Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
Genetic Background	involves: 129S4/SvJae * C57BL/6J * DBA/2 * FVB

Find Mice

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

homeostasis/metabolism

increased circulating alkaline phosphatase level ( J:63878 )

• at 6 months, mutant mice show a 50% increase in alkaline phosphatase levels, suggesting biliary tract dysfunction

increased circulating aspartate transaminase level ( J:63878 )

• at 6 months, mutant mice show a 2.6-fold increase in aspartate aminotransferase levels, suggesting hepatocellular damage

• in contrast, no significant changes in levels of lactate dehydrogenase or alanine aminotransferase are observed

abnormal circulating serum albumin level ( J:63878 )

• at 6 months, mutant mice display a 50% reduction in serum albumin levels

abnormal glucose homeostasis ( J:63878 )

• at 2 months, male mutants fail to suppress hepatic glucose output in response to insulin administration, despite intact insulin signaling in adipose tissue and nearly normal insulin signaling in muscle

increased insulin secretion ( J:63878 )

• at 6 months, female mutants show a have 5- to 6-fold increase in pancreatic insulin content measured in acid-ethanol extracts

hyperglycemia ( J:63878 )

• at 2 months, male mutants exhibit significantly elevated blood glucose in the fed state, despite a 20-fold increase in insulin levels relative to control mice; in contrast, glucagon levels remain unaffected

• at 2 months, male mutants also display a mild hyperglycemia in the fasted state, despite a 7-fold increase in serum insulin levels

• unexpectedly, as mutant mice age, the elevated fasting blood glucose levels progressively decline; by 6 months of age, mutants exhibit fasting hypoglycemia rather than hyperglycemia

increased circulating insulin level ( J:63878 )

• at 2 months, male mutants exhibit an extreme increase in serum insulin levels (20-fold in fed state; 7-fold in fasted state)

impaired glucose tolerance ( J:63878 )

• at 2 months, fasted male mutants display pronounced glucose intolerance

• surprisingly, glucose intolerance is no longer apparent at 6 months

abnormal insulin clearance ( J:63878 )

• in addition to increased insulin secretion, 11-week-old male mutants show a 75% reduction in the C-peptide:insulin ratio, indicating decreased insulin clearance

insulin resistance ( J:63878 )

• at 2 months, random-fed male mutants are severely resistant to the blood glucose-lowering effects of exogenously administered insulin

abnormal lipid homeostasis ( J:63878 )

decreased circulating free fatty acids level ( J:63878 )

• at 2 months, male mutants show a 40-50% reduction in the levels of serum free fatty acids

decreased circulating triglyceride level ( J:63878 )

• at 2 months, male mutants show a 40-50% reduction in the levels of serum triglycerides

increased bile salt level ( J:92861 )

• mutant gallbladders show a notable increase in bile volume

liver/biliary system

enlarged gallbladder ( J:63878 )

• at 6- to 12-months of age, mutant gall bladders appear enlarged

abnormal liver morphology ( J:63878 )

• at 2 months, mutant livers appear a little darker in color, with areas of focal dysplasia and reduced glycogen storage in the parenchyma; no steatosis is observed

• at 6- to 12-months of age, mutant livers display multiple hyperplastic pale nodules scattered throughout all lobes

• by 12 months, the normal lobular structure is disrupted; hyperplastic nodules consist of highly vacuolated cells that compress the adjacent normal tissue, in the absence of fibrosis

abnormal hepatocyte morphology ( J:63878 )

• at 6 months, mutant hepatocytes exhibit a moderate increase in lipid accumulation; only a few electron-dense glycogen granules are observed

small liver ( J:63878 )

• at 2 months, mutant livers are 40% smaller than those of age- and gender-matched controls; liver size decreases significantly with increasing age

abnormal liver physiology ( J:63878 )

• insulin resistance in liver results in elevated expression of PEPCK, the rate-limiting enzyme for gluconeogenesis, and reduced expression of glucokinase and liver pyruvate kinase, two enzymes critical for glucose utilization

• the mutant liver appears to be chronically geared toward glucose production; early insulin signaling events, such as IRS-1 and IRS-2 phosphorylation, are lost

endocrine/exocrine glands

increased pancreatic beta cell mass ( J:63878 , J:92861 )

• at 6 months, increased pancreatic insulin content is associated with a 6-fold increase in pancreatic beta cell mass (J:63878)

• at 6 months, mutant mice show a ~4-fold increase in pancreatic beta cell mass, as a compensatory response to insulin resistance (J:92861)

pancreatic islet hyperplasia ( J:92861 )

• at 6 months, mutant mice show an adaptive islet hyperplastic response to insulin resistance

enlarged gallbladder ( J:63878 )

• at 6- to 12-months of age, mutant gall bladders appear enlarged

increased insulin secretion ( J:63878 )

• at 6 months, female mutants show a have 5- to 6-fold increase in pancreatic insulin content measured in acid-ethanol extracts

cellular

increased mitochondrial size ( J:63878 )

• at 6 months, mutant hepatocytes exhibit giant mitochondria

growth/size/body

enlarged gallbladder ( J:63878 )

• at 6- to 12-months of age, mutant gall bladders appear enlarged

postnatal growth retardation ( J:63878 )

• newborn mutant mice appear normal, nurse successfully, and survive well upon weaning but display a mild growth deficit postweaning

• this moderate growth deficit appears to result from defects in the growth hormone-IGF axis (unpublished data)

Allelic Composition	Insr^tm1Khn/Insr^tm1Khn Tg(Ckmm-cre)5Khn/0
Genetic Background	involves: 129S4/SvJae * C57BL/6J * FVB

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Insr^tm1Khn mutation (1 available); any Insr mutation (94 available)
Tg(Ckmm-cre)5Khn mutation (4 available)

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

adipose tissue

abnormal fat pad morphology ( J:51266 )

• larger than normal fat depots in fat pads, including the perianal, subcutaneous and perigonadal fat pads

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:51266 )

N	• normal serum cholesterol levels • normoglycemia, up to 11 months of age • normal glucose tolerance • normal concentrations of serum insulin

increased fatty acids level ( J:51266 )

• 20% elevation in serum free fatty acids (FFAs)

increased triglyceride level ( J:51266 )

• greater than70% elevated, observed from ages 4 to 11 months

Allelic Composition	Insr^tm1Khn/Insr^tm1Dac Tg(Ckmm-cre)5Khn/0
Genetic Background	involves: 129S4/SvJae * C57BL/6J * FVB

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Insr^tm1Dac mutation (2 available); any Insr mutation (94 available)
Insr^tm1Khn mutation (1 available); any Insr mutation (94 available)
Tg(Ckmm-cre)5Khn mutation (4 available)

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

homeostasis/metabolism

hyperglycemia ( J:51266 )

• in the fed state, incomplete penetrance

increased circulating insulin level ( J:51266 )

Allelic Composition	Insr^tm1Khn/Insr^tm1Khn Tg(Nes-cre)1Kln/0
Genetic Background	involves: 129S4/SvJae * C57BL/6J * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Insr^tm1Khn mutation (1 available); any Insr mutation (94 available)
Tg(Nes-cre)1Kln mutation (4 available)

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

adipose tissue

increased white adipose tissue amount ( J:64790 )

• in females, a two-fold increase in perigonadal adipose tissue is seen

• in males, a 1.5-fold increase in adipose tissue is seen

cellular

oligozoospermia ( J:64790 )

• 30% reduced in epididymal sperm content

behavior/neurological

polyphagia ( J:64790 )

• females exhibit a 20% increase in food intake per gram of body weight

• males did not exhibit any differences in food intake when compared to controls

endocrine/exocrine glands

decreased corpora lutea number ( J:64790 )

decreased tertiary ovarian follicle number ( J:64790 )

• reduced number of antral follicles

abnormal seminiferous tubule morphology ( J:64790 )

• 20% of seminiferous tubules lacked a lumen and had few maturing spermatogonia

• normal seminal vesicles, prostate, and epididymis

decreased Leydig cell number ( J:64790 )

growth/size/body

increased body weight ( J:64790 )

• males do not exhibit weight differences on a standard chow diet, but females exhibit a 10-15% increase over controls

• on a high-fat diet, male mice exhibit a 10% weight increase at 14 weeks of age and females exhibit a 20% increase over controls

homeostasis/metabolism

decreased circulating luteinizing hormone level ( J:64790 )

• 20% of seminiferous tubules lacked a lumen and had few maturing spermatogonia

• normal pituitary morphology and LH content; treatment with lupron indicated that LH is expressed, but not secreted from the pituitary in mutant mice

increased circulating insulin level ( J:64790 )

• at 4-6 months of age, mice exhibit a 1.5 fold increase in circulating insulin levels and females exhibit a 2 fold increase

• normal glucose tolerance

increased circulating leptin level ( J:64790 )

• 1.5 fold increased in males

• normal cholesterol concentrations

• 2.5 fold increased in females

increased circulating triglyceride level ( J:64790 )

• both males and females exhibit a 30% increase in circulating triglycerides

insulin resistance ( J:64790 )

• females exhibit blunted response when injected with insulin and males performed similarly to controls

nervous system

nervous system phenotype ( J:64790 )

N	• brain weights and general brain histology appeared similar to controls

reproductive system

decreased corpora lutea number ( J:64790 )

decreased tertiary ovarian follicle number ( J:64790 )

• reduced number of antral follicles

abnormal seminiferous tubule morphology ( J:64790 )

• 20% of seminiferous tubules lacked a lumen and had few maturing spermatogonia

• normal seminal vesicles, prostate, and epididymis

decreased Leydig cell number ( J:64790 )

abnormal spermatogenesis ( J:64790 )

• impaired

oligozoospermia ( J:64790 )

• 30% reduced in epididymal sperm content

reduced male fertility ( J:64790 )

Allelic Composition	Insr^tm1Khn/Insr^tm1Khn Tg(Nes-cre)1Kln/0
Genetic Background	involves: 129S4/SvJae * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Insr^tm1Khn mutation (1 available); any Insr mutation (94 available)
Tg(Nes-cre)1Kln mutation (4 available)

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

homeostasis/metabolism

abnormal glucose homeostasis ( J:109359 )

• insulin-induced suppression of hepatic glucose productionas assessed with a euglycemic hyperinsulinemic clamp is attenuated

Allelic Composition	Insr^tm1Khn/Insr^tm1Khn Tg(Myhca-cre)1Abel/0
Genetic Background	involves: 129S4/SvJae * FVB

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Insr^tm1Khn mutation (1 available); any Insr mutation (94 available)
Tg(Myhca-cre)1Abel mutation (0 available)

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

cardiovascular system

increased cardiac muscle glycogen level ( J:75348 )

• hearts have 2.3 times the glycogen content of wild-type and insulin administration reduces levels to those seen in wild-type

decreased myocardial fiber size ( J:75348 )

• decrease in cardiomyocyte size, with myocyte length and width reduced by 6 and 9%, respectively

abnormal heart development ( J:75348 )

• exhibit a persistence of the fetal pattern of cardiac metabolism, indicating that the metabolic switch from predominant glucose metabolism, as seen in neonatal hearts, to fatty acid metabolism that characterizes the adult heart, is defective

small heart ( J:75348 )

• 20-30% reduction in size due to reduced cardiomyocyte size

decreased heart left ventricle weight ( J:75348 )

decreased heart left ventricle posterior wall thickness ( J:75348 )

• decrease in LV posterior wall thickness

abnormal cardiovascular system physiology ( J:75348 )

• cardiac power, determined by cardiac output and developed pressure, is modestly reduced

decreased coronary flow rate ( J:75348 )

decreased cardiac output ( J:75348 )

• cardiac output is about 15% lower than in wild-type

abnormal cardiac muscle cell glucose uptake ( J:75348 )

• physiological concentrations of insulin do not cause an increase in myocyte glucose uptake as in wild-type

decreased cardiac muscle cell glucose uptake ( J:75348 )

• decrease in basal glucose uptake in isolated cardiac myocytes

increased cardiac muscle cell glucose uptake ( J:75348 )

• 68% increase in the basal rate of cardiac glucose uptake in intact hearts in vivo and in isolated working hearts

decreased cardiac muscle contractility ( J:75348 )

• exhibit an increase in left ventricular systolic dimension without any change in diastolic dimension, a 29% reduction in fractional shortening, and 12% reduction in ejection fraction

homeostasis/metabolism

abnormal glucose homeostasis ( J:75348 )

• basal rates of glycolysis in hearts are significantly higher than in wild-type, and do not increase further upon insulin treatment

• basal rates of glucose oxidation in isolated hearts are 30% lower than in wild-type, however insulin increases oxidation rates to a similar rate seen in insulin-treated wild-type hearts

increased cardiac muscle glycogen level ( J:75348 )

• hearts have 2.3 times the glycogen content of wild-type and insulin administration reduces levels to those seen in wild-type

abnormal lipid homeostasis ( J:75348 )

• basal rates of palmitate oxidation in isolated hearts are 34% lower than in wild-type and do not change further after insulin stimulation

muscle

increased cardiac muscle glycogen level ( J:75348 )

• hearts have 2.3 times the glycogen content of wild-type and insulin administration reduces levels to those seen in wild-type

decreased myocardial fiber size ( J:75348 )

• decrease in cardiomyocyte size, with myocyte length and width reduced by 6 and 9%, respectively

abnormal cardiac muscle cell glucose uptake ( J:75348 )

• physiological concentrations of insulin do not cause an increase in myocyte glucose uptake as in wild-type

decreased cardiac muscle cell glucose uptake ( J:75348 )

• decrease in basal glucose uptake in isolated cardiac myocytes

increased cardiac muscle cell glucose uptake ( J:75348 )

• 68% increase in the basal rate of cardiac glucose uptake in intact hearts in vivo and in isolated working hearts

decreased cardiac muscle contractility ( J:75348 )

• exhibit an increase in left ventricular systolic dimension without any change in diastolic dimension, a 29% reduction in fractional shortening, and 12% reduction in ejection fraction

cellular

abnormal cardiac muscle cell glucose uptake ( J:75348 )

• physiological concentrations of insulin do not cause an increase in myocyte glucose uptake as in wild-type

decreased cardiac muscle cell glucose uptake ( J:75348 )

• decrease in basal glucose uptake in isolated cardiac myocytes

increased cardiac muscle cell glucose uptake ( J:75348 )

• 68% increase in the basal rate of cardiac glucose uptake in intact hearts in vivo and in isolated working hearts

Allelic Composition	Insr^tm1Khn/Insr^tm1Khn Tg(Slc2a4-cre)546Dac/0
Genetic Background	involves: 129S4/SvJaeSor * C57BL/6 * FVB

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Insr^tm1Khn mutation (1 available); any Insr mutation (94 available)
Tg(Slc2a4-cre)546Dac mutation (0 available)

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

growth/size/body

abnormal lean body mass ( J:169404 )

• diabetic mutants show reduced lean body mass but normal locomotion

decreased body weight ( J:169404 )

• 16-week-old males exhibit a 19% decrease in body weight relative to controls; reduction affects lean and fat mass equally, and plasma leptin levels are normal

• diabetic mutants have significantly lower body weights than controls or non-diabetic mutants

postnatal growth retardation ( J:169404 )

• body weight of mutants is normal as weanlings, but mice show persistent growth retardation from that time point onward

adipose tissue

abnormal brown adipose tissue morphology ( J:169404 )

• tissue shows striking disruption of multilocular structure in mutants; this is more pronounced in diabetic mutants

increased brown fat cell lipid droplet size ( J:169404 )

• size is increased in mutants; this is more pronounced in diabetic mutants

abnormal epididymal fat pad morphology ( J:169404 )

• epididymal white adipose tissue has a heterogeneous appearance compared to controls

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:169404 )

• euglycemic mutants display beta cell hyperplasia, but otherwise islet structure is normal

abnormal pancreatic beta cell morphology ( J:169404 )

• euglycemic mutants display beta cell hyperplasia, but otherwise islet structure is normal

decreased pancreatic beta cell number ( J:169404 )

• diabetic mutants show spotted pattern of loss of insulin immunoreactivity in pancreatic islets

liver/biliary system

decreased liver glycogen level ( J:169404 )

• glycogen depletion in liver is observed only in diabetic mutant animals; non-diabetic mutants have normal-appearing livers

hepatic steatosis ( J:169404 )

• this is observed only in diabetic mutant animals; non-diabetic mutants have normal-appearing livers

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:169404 )

N	• fasting plasma glucagon and beta-hydroxyl butyrate levels are similar to controls

increased circulating free fatty acids level ( J:169404 )

• clamp hyperinsulinemia suppresses free fatty acid levels by 43% but has no effect on GIRKO (Glut4-cre-driven InsR knockout) mutants

increased oxygen consumption ( J:169404 )

• diabetic mutants show increased oxygen consumption when normalized to body weight compared to controls

abnormal glucose homeostasis ( J:169404 )

• during hyperinsulinemic phase of (euglycemic-hyperglycemic) clamp experiments on 13-15 week-old mice, rate of glucose infusion to maintain euglycemia is increased 52% relative to controls (suggesting impaired glucose clearance)

• basal hepatic glucose production is increased by 32% and hyperinsulinemia cannot suppress it (suggesting hepatic insulin resistance)

• glucose disappearance is reduced by 28% and glycolysis is decreased by 33% compared to controls, while glycogen synthesis shows a downward trend

• insulin-dependent glucose uptake is reduced by 34% in muscle

increased circulating glucose level ( J:169404 )

• under basal conditions, mice show slightly elevated blood glucose levels (119 vs 87 mg/dl)

hyperglycemia ( J:169404 )

• at 5 weeks, a subset of mice (male and female) show hyperglycemia in the fed state

• prevalence of diabetes (glycemia > +2 standard deviations) in males increases from 20% at 5 weeks to 25% at 12 weeks and 46% at 24 weeks; in females, diabetes prevalence remains around 10% in 5-12 week-old mice

increased circulating insulin level ( J:169404 )

• subset of mice exhibit hyperinsulinemia in fed and fasted state at 12 weeks

impaired glucose tolerance ( J:169404 )

• at 12-13 weeks, males show mild glucose intolerance

decreased liver glycogen level ( J:169404 )

• glycogen depletion in liver is observed only in diabetic mutant animals; non-diabetic mutants have normal-appearing livers

insulin resistance ( J:169404 )

• 12-13 week old females show mild insulin resistance

behavior/neurological

abnormal circadian feeding behavior ( J:169404 )

• non-diabetic mutants show reduced food consumption during the light phase compared to controls (26% vs 34% in controls)

Allelic Composition	Igf1r^tm1.1Mhz/Igf1r⁺ Insr^tm1Khn/Insr^tm1Khn Tg(Ckmm-cre)5Khn/0
Genetic Background	involves: 129/Sv * 129S4/SvJae * C57BL/6 * FVB

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Igf1r^tm1.1Mhz mutation (0 available); any Igf1r mutation (86 available)
Insr^tm1Khn mutation (1 available); any Insr mutation (94 available)
Tg(Ckmm-cre)5Khn mutation (4 available)

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

mortality/aging

premature death ( J:118987 )

• 3 of 13 mice die by 6 months of age

cardiovascular system

decreased ventricle muscle contractility ( J:118987 )

• at P17, left ventricular fractional shortening is reduced 23% compared to Igf1r^tm1.1Mhz Insr^tm1Khn homozygote controls

respiratory system

abnormal breathing pattern ( J:118987 )

• beginning at 3 months of age, 1 of 13 mice appear to gasp for air

behavior/neurological

decreased locomotor activity ( J:118987 )

• beginning at 3 months of age, 1 of 13 mice exhibit less activity than wild-type mice

muscle

decreased ventricle muscle contractility ( J:118987 )

• at P17, left ventricular fractional shortening is reduced 23% compared to Igf1r^tm1.1Mhz Insr^tm1Khn homozygote controls

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:118987 )

N	• mice exhibit normal glucose homeostasis

Allelic Composition	Igf1r^tm1.1Mhz/Igf1r^tm1.1Mhz Insr^tm1Khn/Insr^tm1Khn Tg(Ckmm-cre)5Khn/0
Genetic Background	involves: 129/Sv * 129S4/SvJae * C57BL/6 * FVB

Find Mice

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

mortality/aging

postnatal lethality, complete penetrance ( J:118987 )

• mice die within the first month usually after birth 2 days after beginning to gasp for air at P16

• death is either spontaneous or precipitated by the stress of routine handling

cardiovascular system

abnormal myocardial fiber morphology ( J:118987 )

• mice exhibit irregular and disrupted sarcomeric Z and M lines and increased mitochondria with central crowding compared to wild-type hearts

decreased myocardial fiber size ( J:118987 )

thin interventricular septum ( J:118987 )

• thin at P17

small heart ( J:118987 )

decreased heart weight ( J:118987 )

• at P8 and P20, heart weights reduced 15% and 25%, respectively, compared to in wild-type mice

• mice exhibit decreased heart weight to body weight

abnormal heart left ventricle morphology ( J:118987 )

• at P17, mice exhibit an increase in left ventricle diameter of 6.7% in diastolic and 57.1% in systolic states

thin ventricular wall ( J:118987 )

• at P17

cardiac interstitial fibrosis ( J:118987 )

dilated cardiomyopathy ( J:118987 )

• at P17

decreased ventricle muscle contractility ( J:118987 )

• at P17, left ventricular fractional shortening is reduced 33% compared to Igf1r^tm1.1Mhz Insr^tm1Khn homozygote controls

decreased heart rate ( J:118987 )

congestive heart failure ( J:118987 )

behavior/neurological

decreased locomotor activity ( J:118987 )

• at P16, mice become less active than wild-type mice

respiratory system

abnormal breathing pattern ( J:118987 )

• at P16, mice gasp for air

growth/size/body

decreased body weight ( J:118987 )

• at P20, mice weigh 15% to 20% less than wild-type mice

postnatal growth retardation ( J:118987 )

• despite normal growth rates during the first two weeks after birth, mice exhibit reduced growth rates during week 3

muscle

abnormal myocardial fiber morphology ( J:118987 )

• mice exhibit irregular and disrupted sarcomeric Z and M lines and increased mitochondria with central crowding compared to wild-type hearts

decreased myocardial fiber size ( J:118987 )

dilated cardiomyopathy ( J:118987 )

• at P17

decreased ventricle muscle contractility ( J:118987 )

• at P17, left ventricular fractional shortening is reduced 33% compared to Igf1r^tm1.1Mhz Insr^tm1Khn homozygote controls

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:118987 )

N	• mice exhibit normal glucose homeostasis

cellular

cardiac interstitial fibrosis ( J:118987 )

Allelic Composition	Igf1r^tm1.1Mhz/Igf1r^tm1.1Mhz Insr^tm1Khn/Insr⁺ Tg(Ckmm-cre)5Khn/0
Genetic Background	involves: 129/Sv * 129S4/SvJae * C57BL/6 * FVB

Find Mice

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

cardiovascular system

cardiovascular system phenotype ( J:118987 )

N	• heart function and morphology is normal

growth/size/body

growth/size/body region phenotype ( J:118987 )

N	• mice exhibit normal growth rates

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:118987 )

N	• mice exhibit normal glucose homeostasis

Allelic Composition	Igf1r^tm1.1Mhz/Igf1r^tm1.1Mhz Insr^tm1Khn/Insr^tm1Khn
Genetic Background	involves: 129/Sv * 129S4/SvJae * C57BL/6 * FVB

Find Mice

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

cardiovascular system

cardiovascular system phenotype ( J:118987 )

N	• heart function and morphology is normal

growth/size/body

growth/size/body region phenotype ( J:118987 )

N	• mice exhibit normal growth rates

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:118987 )

N	• mice exhibit normal glucose homeostasis

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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