All Phenotypes Irs2<tm2Mfw> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Irs2^tm2Mfw
targeted mutation 2, Morris F White
MGI:3497903

Summary

12 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Irs1^tm1Jos/Irs1⁺ Irs2^tm2Mfw/Irs2^tm2Mfw Tg(Ins2-cre)25Mgn/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3510670
cn2	Irs2^tm2Mfw/Irs2^tm2Mfw Tg(Ins2-cre)25Mgn/0 Tg(Ins2-Irs2)13Mfw/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3510675
cn3	Irs2^tm2Mfw/Irs2^tm2Mfw Tg(Ins2-cre)25Mgn/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3510669
cn4	Irs2^tm2Mfw/Irs2^tm2Mfw Irs4^tm1.1Mfw/Y Lepr^tm3(cre)Mgmj/Lepr⁺	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5705239
cn5	Irs2^tm2Mfw/Irs2^tm2Mfw Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA	MGI:3805307
cn6	Irs1^tm1Mfw/Irs1^tm1Mfw Irs2^tm2Mfw/Irs2^tm2Mfw Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA	MGI:3805306
cn7	Foxo1^tm1Rdp/Foxo1^tm1Rdp Irs1^tm1Mfw/Irs1^tm1Mfw Irs2^tm2Mfw/Irs2^tm2Mfw Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA * FVB	MGI:3805304
cn8	Irs1^tm1Mfw/Irs1⁺ Irs2^tm2Mfw/Irs2^tm2Mfw Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA * FVB/N	MGI:4430357
cn9	Irs1^tm2.1Mfw/Irs1^tm2.1Mfw Irs2^tm2Mfw/Irs2^tm2Mfw Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA * FVB/N	MGI:4430358
cn10	Irs1^tm1Mfw/Irs1^tm2.1Mfw Irs2^tm2Mfw/Irs2^tm2Mfw Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA * FVB/N	MGI:4430356
cn11	Irs2^tm2Mfw/Irs2^tm2Mfw Irs4^tm1.1Mfw/Y Tg(Nes-cre)1Kln/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:5705238
cn12	Irs2^tm2Mfw/Irs2^tm2Mfw Tg(Nes-cre)1Kln/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:5705240

Allelic Composition	Irs1^tm1Jos/Irs1⁺ Irs2^tm2Mfw/Irs2^tm2Mfw Tg(Ins2-cre)25Mgn/0
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Irs1^tm1Jos mutation (0 available); any Irs1 mutation (52 available)
Irs2^tm2Mfw mutation (0 available); any Irs2 mutation (37 available)
Tg(Ins2-cre)25Mgn mutation (2 available)

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

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:93415 )

• at 6 months beta cell content is decreased 8-fold

growth/size/body

decreased body weight ( J:93415 )

homeostasis/metabolism

hyperglycemia ( J:93415 )

• diabetes and progressive severe hyperglycemia are seen starting at 4 weeks of age

decreased circulating insulin level ( J:93415 )

• severe, progressive hypoinsulinemia is seen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 2 diabetes mellitus		DOID:9352	OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036	J:93415

Allelic Composition	Irs2^tm2Mfw/Irs2^tm2Mfw Tg(Ins2-cre)25Mgn/0 Tg(Ins2-Irs2)13Mfw/0
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Irs2^tm2Mfw mutation (0 available); any Irs2 mutation (37 available)
Tg(Ins2-cre)25Mgn mutation (2 available)
Tg(Ins2-Irs2)13Mfw mutation (0 available)

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

growth/size/body

increased body weight ( J:93415 )

• compound mutants continue to gain excess weight

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:93415 )

N	• compound mutants do not develop hyperglycemia

Allelic Composition	Irs2^tm2Mfw/Irs2^tm2Mfw Tg(Ins2-cre)25Mgn/0
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Irs2^tm2Mfw mutation (0 available); any Irs2 mutation (37 available)
Tg(Ins2-cre)25Mgn mutation (2 available)

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

pigmentation

abnormal coat/hair pigmentation ( J:93415 )

• mutants closely resemble agouti mice or mice deficient in Pmoc1 or Mcr4

adipose tissue

increased total body fat amount ( J:93415 )

• body fat is increased 2-fold, a disproportionate increase relative to the increase in body weight

behavior/neurological

polydipsia ( J:93415 )

• mutants drink 65% more water than wild-type mice

polyphagia ( J:93415 )

• mutants consume 60% more food than wild-type mice

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:93415 )

• the number of beta cells does not increase from 4 to 8 weeks of age unlike in wild-type mice, however by 6 months beta cell numbers are normal as a result of proliferation of cells that escaped cre mediated recombination

growth/size/body

increased body weight ( J:93415 )

• increased body weight is seen after 4 weeks of age with mutants weighing 30% more than wild-type mice at 32 weeks of age

• lean mass and total body fat are increased relative to wild-type mice

increased body length ( J:93415 )

• mutants are 10% longer than wild-type mice

homeostasis/metabolism

increased circulating glucose level ( J:93415 )

• fasting and random-fed glucose levels are elevated

increased circulating insulin level ( J:93415 )

• serum insulin is increased 2-fold, however pancreatic insulin levels were decreased more than 2-fold

• increased circulating insulin levels are also seen on a low fat diet

increased circulating leptin level ( J:93415 )

• serum leptin is increased 2-fold

impaired glucose tolerance ( J:93415 )

• glucose intolerance is seen on a normal or low fat diet

insulin resistance ( J:93415 )

• glucose clearance rates were decreased about 50% indicating peripheral insulin resistance

integument

abnormal coat/hair pigmentation ( J:93415 )

• mutants closely resemble agouti mice or mice deficient in Pmoc1 or Mcr4

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 2 diabetes mellitus		DOID:9352	OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036	J:93415

Allelic Composition	Irs2^tm2Mfw/Irs2^tm2Mfw Irs4^tm1.1Mfw/Y Lepr^tm3(cre)Mgmj/Lepr⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Irs2^tm2Mfw mutation (0 available); any Irs2 mutation (37 available)
Irs4^tm1.1Mfw mutation (0 available); any Irs4 mutation (5 available)
Lepr^tm3(cre)Mgmj mutation (1 available); any Lepr mutation (122 available)

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

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:221293 )

N	• blood glucose levels are similar to controls

growth/size/body

growth/size/body region phenotype ( J:221293 )

N	• body weight is essentially similar to homozygous Irs2^tm2Mfw / heterozygous Lepr^tm3(cre)Mgmj male mice

Allelic Composition	Irs2^tm2Mfw/Irs2^tm2Mfw Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Irs2^tm2Mfw mutation (0 available); any Irs2 mutation (37 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

homeostasis/metabolism phenotype ( J:137845 )

N	• mice exhibit normal glucose metabolism

Allelic Composition	Irs1^tm1Mfw/Irs1^tm1Mfw Irs2^tm2Mfw/Irs2^tm2Mfw Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Irs1^tm1Mfw mutation (0 available); any Irs1 mutation (52 available)
Irs2^tm2Mfw mutation (0 available); any Irs2 mutation (37 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

increased circulating glucose level ( J:137845 )

• fasting and postprandial

hyperglycemia ( J:137845 )

• by 5 weeks of age

increased circulating insulin level ( J:137845 )

• fasting and postprandial

decreased circulating cholesterol level ( J:137845 )

decreased circulating HDL cholesterol level ( J:137845 )

decreased circulating free fatty acids level ( J:137845 )

impaired glucose tolerance ( J:137845 )

decreased liver glycogen level ( J:137845 )

insulin resistance ( J:137845 )

abnormal triglyceride level ( J:137845 )

decreased circulating triglyceride level ( J:137845 )

• at 3 months of age, triglyceride secretion is decreased 60% compared to in wild-type mice

liver/biliary system

decreased liver glycogen level ( J:137845 )

immune system

increased susceptibility to autoimmune diabetes ( J:137845 )

• mice develop diabetes

growth/size/body

decreased body size ( J:137845 )

Allelic Composition	Foxo1^tm1Rdp/Foxo1^tm1Rdp Irs1^tm1Mfw/Irs1^tm1Mfw Irs2^tm2Mfw/Irs2^tm2Mfw Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA * FVB

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Foxo1^tm1Rdp mutation (2 available); any Foxo1 mutation (32 available)
Irs1^tm1Mfw mutation (0 available); any Irs1 mutation (52 available)
Irs2^tm2Mfw mutation (0 available); any Irs2 mutation (37 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

homeostasis/metabolism phenotype ( J:137845 )

N	• unlike in Irs1 and Irs2 double null mice, fasting glucose, insulin, and adiponectin levels, insulin resistance, fed glucose levels, hepatic glycogen levels, and glucose tolerance are normal

decreased circulating cholesterol level ( J:137845 )

decreased circulating HDL cholesterol level ( J:137845 )

• mice exhibit a partial recovery of plasma HDL cholesterol levels compared to in Irs1 and Irs2 double knockout mice

decreased circulating free fatty acids level ( J:137845 )

abnormal triglyceride level ( J:137845 )

• triglyceride secretion is decreased compared to in wild-type mice but increased compared to in Irs1 and Irs2 double knockout mice

decreased circulating triglyceride level ( J:137845 )

Allelic Composition	Irs1^tm1Mfw/Irs1⁺ Irs2^tm2Mfw/Irs2^tm2Mfw Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA * FVB/N

Find Mice

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

homeostasis/metabolism

impaired glucose tolerance ( J:156999 )

• significantly glucose intolerant

Allelic Composition	Irs1^tm2.1Mfw/Irs1^tm2.1Mfw Irs2^tm2Mfw/Irs2^tm2Mfw Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Irs1^tm2.1Mfw mutation (0 available); any Irs1 mutation (52 available)
Irs2^tm2Mfw mutation (0 available); any Irs2 mutation (37 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

increased circulating insulin level ( J:156999 )

• fasting insulin concentration are elevated

impaired glucose tolerance ( J:156999 )

• significantly glucose intolerant

Allelic Composition	Irs1^tm1Mfw/Irs1^tm2.1Mfw Irs2^tm2Mfw/Irs2^tm2Mfw Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Irs1^tm1Mfw mutation (0 available); any Irs1 mutation (52 available)
Irs1^tm2.1Mfw mutation (0 available); any Irs1 mutation (52 available)
Irs2^tm2Mfw mutation (0 available); any Irs2 mutation (37 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

increased circulating insulin level ( J:156999 )

• fasting and fed insulin concentrations are elevated

impaired glucose tolerance ( J:156999 )

• severe glucose intolerance

insulin resistance ( J:156999 )

• significant insulin resistance

Allelic Composition	Irs2^tm2Mfw/Irs2^tm2Mfw Irs4^tm1.1Mfw/Y Tg(Nes-cre)1Kln/?
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

Find Mice

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

growth/size/body

increased body weight ( J:221293 )

• 60% heavier than controls

• 20% heavier than Irs2^tm2Mfw / Tg(Nes-cre)1Kln male mice

adipose tissue

abnormal adipose tissue amount ( J:221293 )

• increased adipose tissue relative to Irs2^tm2Mfw / Tg(Nes-cre)1Kln male mice

increased brown fat cell lipid droplet size ( J:221293 )

• larger lipid filled vacuoles in brown adipose tissue compared to Irs2^tm2Mfw / Tg(Nes-cre)1Kln male mice

• resembles white adipose tissue

liver/biliary system

hepatic steatosis ( J:221293 )

homeostasis/metabolism

increased circulating leptin level ( J:221293 )

• greatly elevated

decreased oxygen consumption ( J:221293 )

abnormal glucose homeostasis ( J:221293 )

increased circulating glucose level ( J:221293 )

• ad libitum feeding results in increased blood glucose

increased fasting circulating glucose level ( J:221293 )

• dramatically elevated at 3 months

increased circulating insulin level ( J:221293 )

• 5 fold elevation

impaired glucose tolerance ( J:221293 )

• dramatically impaired at 3 months

insulin resistance ( J:221293 )

• at 3 months and persisting to at least 9 months

decreased basal metabolism ( J:221293 )

• reduced heat production

behavior/neurological

increased food intake ( J:221293 )

• food intake increased 10% more than in Irs2^tm2Mfw / Tg(Nes-cre)1Kln male mice

Allelic Composition	Irs2^tm2Mfw/Irs2^tm2Mfw Tg(Nes-cre)1Kln/?
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Irs2^tm2Mfw mutation (0 available); any Irs2 mutation (37 available)
Tg(Nes-cre)1Kln mutation (4 available)

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

homeostasis/metabolism

increased circulating leptin level ( J:221293 )

decreased oxygen consumption ( J:221293 )

abnormal glucose homeostasis ( J:221293 )

increased circulating glucose level ( J:221293 )

• ad libitum feeding results in insignificantly increased blood glucose

increased fasting circulating glucose level ( J:221293 )

• slightly elevated at 3 months

increased circulating insulin level ( J:221293 )

• slightly increased

impaired glucose tolerance ( J:221293 )

• slight impairment at 3 months

insulin resistance ( J:221293 )

• at 9 months

decreased basal metabolism ( J:221293 )

• reduced heat production

behavior/neurological

increased food intake ( J:221293 )

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