Strain Name:

B6.129S4(FVB)-Insrtm1Khn/J

Stock Number:

006955

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Availability:

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These IRlox mutant mice have loxP sites flanking exon 4 of the targeted gene. When bred to Cre-recombinase expressing mice, offspring will have a deletion of exon 4 in the cre expressing tissue(s). These "floxed" mice may be useful in studying insulin receptor function in several different tissues (including pancreas, liver, and skeletal muscle), as well as diabetes and glucose regulation.

Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Additional information on Congenic nomenclature.
Mating SystemHomozygote x Homozygote         (Female x Male)   16-FEB-11
Specieslaboratory mouse
GenerationN11+ (09-AUG-10)
Generation Definitions
 
Donating Investigator C. Ronald Kahn,   Joslin Diabetes Center

Description
Mice homozygous for this IRlox allele are viable and fertile. These mutant mice have loxP sites flanking exon 4 of the targeted gene. When bred to Cre-recombinase expressing mice, offspring will have a deletion of exon 4 in the cre expressing tissue(s). These "floxed" mice may be useful in studying insulin receptor function in several different tissues (including pancreas, liver, and skeletal muscle), as well as diabetes and glucose regulation.

For example, when crossed to a strain expressing Cre recombinase in the central and peripheral nervous system (see Stock No. 003771), this mutant mouse strain may be useful in studies of glucose homeostasis.

When crossed to a strain expressing Cre recombinase in skeletal and cardiac muscle (see Stock No. 006475), this mutant mouse strain may be useful in studies of diabetes.

When crossed to a strain expressing Cre recombinase in the liver (see Stock No. 003574), this mutant mouse strain may be useful in studies of insulin resistance.

When crossed to a strain expressing Cre recombinase in pancreatic beta cells (see Stock No. 003573), this mutant mouse strain may be useful in studies of diabetes.

Development
A targeting vector was designed to insert a loxP-flanked neomycin cassette downstream of exon 4, as well as a single loxP site 80 bp downstream of exon 4 of the targeted gene. The construct was electroporated into the 129S4/SvJae-derived J1 embryonic stem (ES) cells. ES cell were transiently transfected with a Cre-recombinase plasmid to delete the selection cassette, leaving single loxP sites upstream and downstream of exon 4. Correctly targeted ES cells were injected into C57BL/6J blastocysts, which were injected into pseudopregnant CD-1 foster females. The resulting mutant mice (IRlox) were backcrossed to C57BL/6J inbred mice. At some point, mice were bred to Mck-Cre transgenic mice (FVB genetic background, see Stock No. 006405). The double mutants were backcrossed for 10 generations to C57BL/6 mice and then selected for the IRlox (and against the transgene) prior to arrival at The Jackson Laboratory.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Insr
002939   B6.129S4-Insrtm1Dac/J
002426   B6;129S4-Insrtm1Dac/J
View Strains carrying other alleles of Insr     (2 strains)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Diabetes Mellitus, Insulin-Resistant, with Acanthosis Nigricans   (INSR)
Donohue Syndrome   (INSR)
Hyperinsulinemic Hypoglycemia, Familial, 5; HHF5   (INSR)
Pineal Hyperplasia, Insulin-Resistant Diabetes Mellitus, and Somatic Abnormalities   (INSR)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.

Insrtm1Khn/Insrtm1Dac Tg(Ckmm-cre)5Khn/0

        involves: 129S4/SvJae * C57BL/6J * FVB   (conditional)
  • homeostasis/metabolism phenotype
  • hyperglycemia
    • in the fed state, incomplete penetrance   (MGI Ref ID J:51266)
  • increased circulating insulin level   (MGI Ref ID J:51266)

Insrtm1Khn/Insrtm1Khn Tg(Alb-cre)21Mgn/0

        involves: 129S4/SvJae * C57BL/6J * DBA/2 * FVB   (conditional)
  • homeostasis/metabolism phenotype
  • abnormal circulating serum albumin level
    • at 6 months, mutant mice display a 50% reduction in serum albumin levels   (MGI Ref ID J:63878)
  • abnormal glucose homeostasis
    • 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   (MGI Ref ID J:63878)
    • abnormal insulin clearance
      • 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   (MGI Ref ID J:63878)
    • hyperglycemia
      • 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   (MGI Ref ID J:63878)
      • at 2 months, male mutants also display a mild hyperglycemia in the fasted state, despite a 7-fold increase in serum insulin levels   (MGI Ref ID J:63878)
      • 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   (MGI Ref ID J:63878)
    • impaired glucose tolerance
      • at 2 months, fasted male mutants display pronounced glucose intolerance   (MGI Ref ID J:63878)
      • surprisingly, glucose intolerance is no longer apparent at 6 months   (MGI Ref ID J:63878)
    • increased circulating insulin level
      • at 2 months, male mutants exhibit an extreme increase in serum insulin levels (20-fold in fed state; 7-fold in fasted state)   (MGI Ref ID J:63878)
    • increased insulin secretion
      • at 6 months, female mutants show a have 5- to 6-fold increase in pancreatic insulin content measured in acid-ethanol extracts   (MGI Ref ID J:63878)
    • insulin resistance
      • at 2 months, random-fed male mutants are severely resistant to the blood glucose-lowering effects of exogenously administered insulin   (MGI Ref ID J:63878)
  • abnormal lipid homeostasis   (MGI Ref ID J:63878)
    • decreased circulating free fatty acid level
      • at 2 months, male mutants show a 40-50% reduction in the levels of serum free fatty acids   (MGI Ref ID J:63878)
    • decreased circulating triglyceride level
      • at 2 months, male mutants show a 40-50% reduction in the levels of serum triglycerides   (MGI Ref ID J:63878)
    • increased bile salt level
      • mutant gallbladders show a notable increase in bile volume   (MGI Ref ID J:92861)
  • increased circulating alkaline phosphatase level
    • at 6 months, mutant mice show a 50% increase in alkaline phosphatase levels, suggesting biliary tract dysfunction   (MGI Ref ID J:63878)
  • increased circulating aspartate transaminase level
    • at 6 months, mutant mice show a 2.6-fold increase in aspartate aminotransferase levels, suggesting hepatocellular damage   (MGI Ref ID J:63878)
    • in contrast, no significant changes in levels of lactate dehydrogenase or alanine aminotransferase are observed   (MGI Ref ID J:63878)
  • liver/biliary system phenotype
  • abnormal liver morphology
    • 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   (MGI Ref ID J:63878)
    • at 6- to 12-months of age, mutant livers display multiple hyperplastic pale nodules scattered throughout all lobes   (MGI Ref ID J:63878)
    • 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   (MGI Ref ID J:63878)
    • abnormal hepatocyte morphology
      • at 6 months, mutant hepatocytes exhibit a moderate increase in lipid accumulation; only a few electron-dense glycogen granules are observed   (MGI Ref ID J:63878)
    • small liver
      • at 2 months, mutant livers are 40% smaller than those of age- and gender-matched controls; liver size decreases significantly with increasing age   (MGI Ref ID J:63878)
  • abnormal liver physiology
    • 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   (MGI Ref ID J:63878)
    • 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   (MGI Ref ID J:63878)
  • enlarged gallbladder
    • at 6- to 12-months of age, mutant gall bladders appear enlarged   (MGI Ref ID J:63878)
  • endocrine/exocrine gland phenotype
  • enlarged gallbladder
    • at 6- to 12-months of age, mutant gall bladders appear enlarged   (MGI Ref ID J:63878)
  • increased insulin secretion
    • at 6 months, female mutants show a have 5- to 6-fold increase in pancreatic insulin content measured in acid-ethanol extracts   (MGI Ref ID J:63878)
  • increased pancreatic beta cell mass
    • at 6 months, increased pancreatic insulin content is associated with a 6-fold increase in pancreatic beta cell mass   (MGI Ref ID J:63878)
    • at 6 months, mutant mice show a ~4-fold increase in pancreatic beta cell mass, as a compensatory response to insulin resistance   (MGI Ref ID J:92861)
  • pancreatic islet hyperplasia
    • at 6 months, mutant mice show an adaptive islet hyperplastic response to insulin resistance   (MGI Ref ID J:92861)
  • cellular phenotype
  • increased mitochondria size
    • at 6 months, mutant hepatocytes exhibit giant mitochondria   (MGI Ref ID J:63878)
  • growth/size/body phenotype
  • postnatal growth retardation
    • newborn mutant mice appear normal, nurse successfully, and survive well upon weaning but display a mild growth deficit postweaning   (MGI Ref ID J:63878)
    • this moderate growth deficit appears to result from defects in the growth hormone-IGF axis (unpublished data)   (MGI Ref ID J:63878)

Insrtm1Khn/Insrtm1Khn Tg(Alb-cre)21Mgn/0

        involves: 129S4/SvJae * C57BL/6 * DBA/2   (conditional)
  • homeostasis/metabolism phenotype
  • decreased circulating glucose level
    • at 10 to 12 months of age   (MGI Ref ID J:121640)
  • hyperglycemia
    • while mice display normoglycemia during the first 3 weeks of life, at 4 weeks mice develop hypoglycemia that lasts until week 6   (MGI Ref ID J:121640)
  • impaired glucose tolerance   (MGI Ref ID J:121640)
  • increased circulating insulin level   (MGI Ref ID J:121640)
  • insulin resistance   (MGI Ref ID J:121640)
  • endocrine/exocrine gland phenotype
  • increased pancreatic beta cell mass
    • 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   (MGI Ref ID J:121640)
    • 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   (MGI Ref ID J:121640)

Insrtm1Khn/Insrtm1Khn Tg(Alb-cre)21Mgn/0 Tg(Ins2-cre)25Mgn/0

        involves: 129S4/SvJae * C57BL/6 * DBA/2   (conditional)
  • mortality/aging
  • premature death
    • 82% of mice die by 6 weeks of age with some mice surviving a few weeks longer   (MGI Ref ID J:121640)
  • homeostasis/metabolism phenotype
  • decreased insulin secretion   (MGI Ref ID J:121640)
  • hyperglycemia
    • mice develop hypoglycemia at 2 weeks of age that rapidly worsens by 6 weeks of age   (MGI Ref ID J:121640)
    • mice exhibit high fasting glucose serum levels   (MGI Ref ID J:121640)
  • impaired glucose tolerance   (MGI Ref ID J:121640)
  • increased circulating insulin level   (MGI Ref ID J:121640)
  • insulin resistance   (MGI Ref ID J:121640)
  • endocrine/exocrine gland phenotype
  • decreased insulin secretion   (MGI Ref ID J:121640)
  • renal/urinary system phenotype
  • polyuria
    • during terminal stages   (MGI Ref ID J:121640)
  • behavior/neurological phenotype
  • polydipsia
    • during terminal stages   (MGI Ref ID J:121640)
  • digestive/alimentary phenotype
  • *normal* digestive/alimentary phenotype
    • unlike mice null for Insr in beta cells mice, islet cell mass is not increased despite similar levels of elevated insulin levels   (MGI Ref ID J:121640)
  • growth/size/body phenotype
  • decreased body weight
    • mice develop severe diabetes and loss 30% of their body weight in terminal stages   (MGI Ref ID J:121640)

Insrtm1Khn/Insrtm1Khn Tg(Ckmm-cre)5Khn/0

        involves: 129S4/SvJae * C57BL/6J * FVB   (conditional)
  • adipose tissue phenotype
  • abnormal fat pad morphology
    • larger than normal fat depots in fat pads, including the perianal, subcutaneous and perigonadal fat pads   (MGI Ref ID J:51266)
  • homeostasis/metabolism phenotype
  • *normal* homeostasis/metabolism phenotype
    • normal serum cholesterol levels   (MGI Ref ID J:51266)
    • normoglycemia, up to 11 months of age   (MGI Ref ID J:51266)
    • normal glucose tolerance   (MGI Ref ID J:51266)
    • normal concentrations of serum insulin   (MGI Ref ID J:51266)
    • increased fatty acid level
      • 20% elevation in serum free fatty acids (FFAs)   (MGI Ref ID J:51266)
    • increased triglyceride level
      • greater than70% elevated, observed from ages 4 to 11 months   (MGI Ref ID J:51266)

Insrtm1Khn/Insrtm1Khn Tg(Ckmm-cre)5Khn/0

        involves: 129S4/SvJae * C57BL/6 * FVB   (conditional)
  • cardiovascular system phenotype
  • *normal* cardiovascular system phenotype
    • heart function and morphology is normal   (MGI Ref ID J:118987)
  • growth/size/body phenotype
  • *normal* growth/size/body phenotype
    • mice exhibit normal growth rates   (MGI Ref ID J:118987)
  • homeostasis/metabolism phenotype
  • *normal* homeostasis/metabolism phenotype
    • mice exhibit normal glucose homeostasis   (MGI Ref ID J:118987)

Insrtm1Khn/Insrtm1Khn Tg(Ins2-cre)25Mgn/0

        involves: 129S4/SvJae * C57BL/6 * DBA/2   (conditional)
  • mortality/aging
  • increased sensitivity to induced morbidity/mortality
    • when fed a high fat diet, 30% of mice die by 16 weeks   (MGI Ref ID J:121640)
  • premature death
    • some mice die due to severe hyperglycemia   (MGI Ref ID J:121640)
  • homeostasis/metabolism phenotype
  • decreased insulin secretion   (MGI Ref ID J:121640)
  • hyperglycemia
    • mice exhibit an increase in serum glucose level on a regular diet and a severe increase when fed a high fat diet   (MGI Ref ID J:121640)
  • impaired glucose tolerance
    • mice exhibit impaired glucose tolerance on a normal diet and severe intolerance when fed a high fat diet   (MGI Ref ID J:121640)
    • however, mice are not insulin resistant   (MGI Ref ID J:121640)
  • endocrine/exocrine gland phenotype
  • decreased insulin secretion   (MGI Ref ID J:121640)
  • decreased pancreatic beta cell mass
    • mice exhibit decreased beta cell mass when fed a normal or high fat diet   (MGI Ref ID J:121640)

Insrtm1Khn/Insrtm1Khn Tg(Nes-cre)1Kln/0

        involves: 129S4/SvJae * C57BL/6J * SJL   (conditional)
  • adipose tissue phenotype
  • increased white adipose tissue amount
    • in females, a two-fold increase in perigonadal adipose tissue is seen   (MGI Ref ID J:64790)
    • in males, a 1.5-fold increase in adipose tissue is seen   (MGI Ref ID J:64790)
  • behavior/neurological phenotype
  • polyphagia
    • females exhibit a 20% increase in food intake per gram of body weight   (MGI Ref ID J:64790)
    • males did not exhibit any differences in food intake when compared to controls   (MGI Ref ID J:64790)
  • endocrine/exocrine gland phenotype
  • abnormal seminiferous tubule morphology
    • 20% of seminiferous tubules lacked a lumen and had few maturing spermatogonia   (MGI Ref ID J:64790)
    • normal seminal vesicles, prostate, and epididymis   (MGI Ref ID J:64790)
    • Leydig cell hypoplasia   (MGI Ref ID J:64790)
  • decreased corpora lutea number   (MGI Ref ID J:64790)
  • impaired ovarian folliculogenesis
    • reduced number of antral follicles   (MGI Ref ID J:64790)
  • growth/size/body phenotype
  • increased body weight
    • males do not exhibit weight differences on a standard chow diet, but females exhibit a 10-15% increase over controls   (MGI Ref ID J:64790)
    • 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   (MGI Ref ID J:64790)
  • homeostasis/metabolism phenotype
  • decreased circulating luteinizing hormone level
    • 20% of seminiferous tubules lacked a lumen and had few maturing spermatogonia   (MGI Ref ID J:64790)
    • normal pituitary morphology and LH content; treatment with lupron indicated that LH is expressed, but not secreted from the pituitary in mutant mice   (MGI Ref ID J:64790)
  • increased circulating insulin level
    • at 4-6 months of age, mice exhibit a 1.5 fold increase in circulating insulin levels and females exhibit a 2 fold increase   (MGI Ref ID J:64790)
    • normal glucose tolerance   (MGI Ref ID J:64790)
  • increased circulating leptin level
    • 2.5 fold increased in females   (MGI Ref ID J:64790)
    • 1.5 fold increased in males   (MGI Ref ID J:64790)
    • normal cholesterol concentrations   (MGI Ref ID J:64790)
  • increased circulating triglyceride level
    • both males and females exhibit a 30% increase in circulating triglycerides   (MGI Ref ID J:64790)
  • insulin resistance
    • females exhibit blunted response when injected with insulin and males performed similarly to controls   (MGI Ref ID J:64790)
  • nervous system phenotype
  • *normal* nervous system phenotype
    • brain weights and general brain histology appeared similar to controls   (MGI Ref ID J:64790)
  • reproductive system phenotype
  • abnormal seminiferous tubule morphology
    • 20% of seminiferous tubules lacked a lumen and had few maturing spermatogonia   (MGI Ref ID J:64790)
    • normal seminal vesicles, prostate, and epididymis   (MGI Ref ID J:64790)
    • Leydig cell hypoplasia   (MGI Ref ID J:64790)
  • abnormal spermatogenesis
    • oligozoospermia
      • 30% reduced in epididymal sperm content   (MGI Ref ID J:64790)
  • decreased corpora lutea number   (MGI Ref ID J:64790)
  • impaired ovarian folliculogenesis
    • reduced number of antral follicles   (MGI Ref ID J:64790)
  • reduced male fertility   (MGI Ref ID J:64790)

Insrtm1Khn/Insrtm1Khn Tg(Nes-cre)1Kln/0

        involves: 129S4/SvJae * C57BL/6 * SJL   (conditional)
  • homeostasis/metabolism phenotype
  • abnormal glucose homeostasis
    • insulin-induced suppression of hepatic glucose productionas assessed with a euglycemic hyperinsulinemic clamp is attenuated   (MGI Ref ID J:109359)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Diabetes and Obesity Research
Insulin Receptors and Growth Factors

Research Tools
Cre-lox System
      loxP-flanked Sequences
Diabetes and Obesity Research
      loxP

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Insrtm1Khn
Allele Name targeted mutation 1, Ronald Kahn
Allele Type Targeted (Conditional ready (e.g. floxed), No functional change)
Common Name(s) IR(lox); IRLox; IRflox; IRlox; Insrflox;
Mutation Made By C. Ronald Kahn,   Joslin Diabetes Center
Strain of Origin129S4/SvJae
Gene Symbol and Name Insr, insulin receptor
Chromosome 8
Gene Common Name(s) 4932439J01Rik; CD220; D630014A15Rik; HHF5; IR; IR-A; IR-B; RIKEN cDNA 4932439J01 gene; RIKEN cDNA D630014A15 gene;
General Note In conjunction with Tg(Mycha-cre)1Abel, this allele is knocked out specifically in cardiac muscle. The resulting mice are referred to as "Cardiac-specific insulin receptor knockout mice" or CIRKO.

In conjunction with Tg(Ckmm-cre)5Khn, this allele is disrupted specifically in skeletal muscle. The resulting mice are referred to as "Muscle-specific insulin receptor knockout mice" or MIRKO.

Molecular Note Exon 4 was left flanked by single loxP sites after a downstream floxed neo cassette was removed via in vitro cre mediated recombination. Deletion of the resultant floxed fragment will result in a frameshift mutation that introduces a stop codon. Translation, if it were to occur, would putatively produce a truncated peptide consisting of 308 amino terminal residues and lacking the high affinity binding site, transmembrane domain, and kinase domain. [MGI Ref ID J:51266]

Genotyping

Genotyping Information

Genotyping Protocols

Generic Neo Melt Curve Analysis, Melt Curve Analysis
Insrtm1Khn, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Bruning JC; Michael MD; Winnay JN; Hayashi T; Horsch D; Accili D; Goodyear LJ; Kahn CR. 1998. A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol Cell 2(5):559-69. [PubMed: 9844629]  [MGI Ref ID J:51266]

Additional References

Insrtm1Khn related

Barger JL; Walford RL; Weindruch R. 2003. The retardation of aging by caloric restriction: its significance in the transgenic era. Exp Gerontol 38(11-12):1343-51. [PubMed: 14698815]  [MGI Ref ID J:87701]

Bartels ED; Nielsen JM; Hellgren LI; Ploug T; Nielsen LB. 2009. Cardiac expression of microsomal triglyceride transfer protein is increased in obesity and serves to attenuate cardiac triglyceride accumulation. PLoS ONE 4(4):e5300. [PubMed: 19390571]  [MGI Ref ID J:148263]

Baumgartl J; Baudler S; Scherner M; Babaev V; Makowski L; Suttles J; McDuffie M; Tobe K; Kadowaki T; Fazio S; Kahn CR; Hotamisligil GS; Krone W; Linton M; Bruning JC. 2006. Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis. Cell Metab 3(4):247-56. [PubMed: 16581002]  [MGI Ref ID J:129654]

Belke DD; Betuing S; Tuttle MJ; Graveleau C; Young ME; Pham M; Zhang D; Cooksey RC; McClain DA; Litwin SE; Taegtmeyer H; Severson D; Kahn CR; Abel ED. 2002. Insulin signaling coordinately regulates cardiac size, metabolism, and contractile protein isoform expression. J Clin Invest 109(5):629-39. [PubMed: 11877471]  [MGI Ref ID J:75348]

Biddinger SB; Haas JT; Yu BB; Bezy O; Jing E; Zhang W; Unterman TG; Carey MC; Kahn CR. 2008. Hepatic insulin resistance directly promotes formation of cholesterol gallstones. Nat Med 14(7):778-82. [PubMed: 18587407]  [MGI Ref ID J:137829]

Biddinger SB; Hernandez-Ono A; Rask-Madsen C; Haas JT; Aleman JO; Suzuki R; Scapa EF; Agarwal C; Carey MC; Stephanopoulos G; Cohen DE; King GL; Ginsberg HN; Kahn CR. 2008. Hepatic insulin resistance is sufficient to produce dyslipidemia and susceptibility to atherosclerosis. Cell Metab 7(2):125-34. [PubMed: 18249172]  [MGI Ref ID J:132137]

Biddinger SB; Miyazaki M; Boucher J; Ntambi JM; Kahn CR. 2006. Leptin suppresses stearoyl-CoA desaturase 1 by mechanisms independent of insulin and sterol regulatory element-binding protein-1c. Diabetes 55(7):2032-41. [PubMed: 16804073]  [MGI Ref ID J:111873]

Bluher M; Kahn BB; Kahn CR. 2003. Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299(5606):572-4. [PubMed: 12543978]  [MGI Ref ID J:82237]

Bluher M; Michael MD; Peroni OD; Ueki K; Carter N; Kahn BB; Kahn CR. 2002. Adipose tissue selective insulin receptor knockout protects against obesity and obesity-related glucose intolerance. Dev Cell 3(1):25-38. [PubMed: 12110165]  [MGI Ref ID J:108968]

Bluher M; Patti ME; Gesta S; Kahn BB; Kahn CR. 2004. Intrinsic heterogeneity in adipose tissue of fat-specific insulin receptor knock-out mice is associated with differences in patterns of gene expression. J Biol Chem 279(30):31891-901. [PubMed: 15131119]  [MGI Ref ID J:91903]

Bluher M; Wilson-Fritch L; Leszyk J; Laustsen PG; Corvera S; Kahn CR. 2004. Role of insulin action and cell size on protein expression patterns in adipocytes. J Biol Chem 279(30):31902-9. [PubMed: 15131120]  [MGI Ref ID J:91902]

Boucher J; Mori MA; Lee KY; Smyth G; Liew CW; Macotela Y; Rourk M; Bluher M; Russell SJ; Kahn CR. 2012. Impaired thermogenesis and adipose tissue development in mice with fat-specific disruption of insulin and IGF-1 signalling. Nat Commun 3:902. [PubMed: 22692545]  [MGI Ref ID J:205635]

Boudina S; Bugger H; Sena S; O'Neill BT; Zaha VG; Ilkun O; Wright JJ; Mazumder PK; Palfreyman E; Tidwell TJ; Theobald H; Khalimonchuk O; Wayment B; Sheng X; Rodnick KJ; Centini R; Chen D; Litwin SE; Weimer BE; Abel ED. 2009. Contribution of impaired myocardial insulin signaling to mitochondrial dysfunction and oxidative stress in the heart. Circulation 119(9):1272-83. [PubMed: 19237663]  [MGI Ref ID J:166005]

Brothers KJ; Wu S; DiVall SA; Messmer MR; Kahn CR; Miller RS; Radovick S; Wondisford FE; Wolfe A. 2010. Rescue of obesity-induced infertility in female mice due to a pituitary-specific knockout of the insulin receptor. Cell Metab 12(3):295-305. [PubMed: 20816095]  [MGI Ref ID J:166365]

Bruning JC; Gautam D; Burks DJ; Gillette J; Schubert M; Orban PC; Klein R; Krone W; Muller-Wieland D; Kahn CR. 2000. Role of brain insulin receptor in control of body weight and reproduction [see comments] Science 289(5487):2122-5. [PubMed: 11000114]  [MGI Ref ID J:64790]

Burcelin R; Crivelli V; Perrin C; Da Costa A; Mu J; Kahn BB; Birnbaum MJ; Kahn CR; Vollenweider P; Thorens B. 2003. GLUT4, AMP kinase, but not the insulin receptor, are required for hepatoportal glucose sensor-stimulated muscle glucose utilization. J Clin Invest 111(10):1555-62. [PubMed: 12750405]  [MGI Ref ID J:134630]

Cariou B; Postic C; Boudou P; Burcelin R; Kahn CR; Girard J; Burnol AF; Mauvais-Jarvis F. 2004. Cellular and molecular mechanisms of adipose tissue plasticity in muscle insulin receptor knockout mice. Endocrinology 145(4):1926-32. [PubMed: 14684612]  [MGI Ref ID J:88697]

Cohen SE; Kokkotou E; Biddinger SB; Kondo T; Gebhardt R; Kratzsch J; Mantzoros CS; Kahn CR. 2007. High circulating leptin receptors with normal leptin sensitivity in liver-specific insulin receptor knock-out (LIRKO) mice. J Biol Chem 282(32):23672-8. [PubMed: 17556363]  [MGI Ref ID J:124577]

Diggs-Andrews KA; Zhang X; Song Z; Daphna-Iken D; Routh VH; Fisher SJ. 2010. Brain insulin action regulates hypothalamic glucose sensing and the counterregulatory response to hypoglycemia. Diabetes 59(9):2271-80. [PubMed: 20547974]  [MGI Ref ID J:169634]

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Yoon JC; Puigserver P; Chen G; Donovan J; Wu Z; Rhee J; Adelmant G; Stafford J; Kahn CR; Granner DK; Newgard CB; Spiegelman BM. 2001. Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 413(6852):131-8. [PubMed: 11557972]  [MGI Ref ID J:120036]

Zabolotny JM; Haj FG; Kim YB; Kim HJ; Shulman GI; Kim JK; Neel BG; Kahn BB. 2004. Transgenic overexpression of protein-tyrosine phosphatase 1B in muscle causes insulin resistance, but overexpression with leukocyte antigen-related phosphatase does not additively impair insulin action. J Biol Chem 279(23):24844-51. [PubMed: 15031294]  [MGI Ref ID J:122895]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX10

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice are bred.
Mating SystemHomozygote x Homozygote         (Female x Male)   16-FEB-11
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $232.00Female or MaleHomozygous for Insrtm1Khn  
Price per Pair (US dollars $)Pair Genotype
$464.00Homozygous for Insrtm1Khn x Homozygous for Insrtm1Khn  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $301.60Female or MaleHomozygous for Insrtm1Khn  
Price per Pair (US dollars $)Pair Genotype
$603.20Homozygous for Insrtm1Khn x Homozygous for Insrtm1Khn  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.


See Terms of Use tab for General Terms and Conditions


The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
Ordering Information
JAX® Mice
Surgical and Preconditioning Services
JAX® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use


General Terms and Conditions


Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:207-288-6470

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.


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