Strain Name:

B6;129-Igf1rtm2Arge/J

Stock Number:

012251

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Availability:

Repository- Live

These floxed mutant mice possess loxP sites flanking exon 3 of the Igf1r gene. This strain may be useful for generating conditional mutations for studies of mammary tumorigenesis, myelination and bone development.

Description

Strain Information

Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Mating SystemHomozygote x Homozygote         (Female x Male)   04-JUN-11
Specieslaboratory mouse
GenerationF?+N2F8 (11-DEC-13)
Generation Definitions
 
Donating Investigator Argiris Efstratiadis,   Academy of Athens

Description
These mice possess loxP sites on either side of exon 3 of the targeted gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 3 deleted in the cre-expressing tissue(s).

When crossed with a mouse overexpressing constitutively active Kras and expressing mammary gland specific Cre recombinase, this IGF1RLox mutant mouse strain may be useful in studies of mammary tumorigenesis (Proc Natl Acad Sci U S A 2009 Feb 17;106(7):2359-64).

When bred to a strain with Cre recombinase expression in the CNS, this mutant mouse strain may be useful in studies of myelination (Genesis 2000 Feb;26(2):133-5).

When bred to a strain carrying Tg(BGLAP-cre)1Clem (Stock No. 019509), Cre recombinase expression in osteoblasts results in abnormal bone matrix mineralization (J Biol Chem 2002 Nov 15;277(46):44005-12).

When bred to a strain carrying Tg(Tek-cre)1Ywa (Stock No. 008863), Cre recombinase expression in endothelial cells results in impaired endothelial regeneration following arterial injury.

Development
A targeting vector containing a loxP site flanked neo selection cassette was utilized in the construction of this mutant. This selection cassette was inserted downstream of exon 3 of the targeted gene, and another loxP site was inserted upstream of exon 3. This construct was electroporated into 129 derived embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a Cre expression plasmid for the purpose of removing the selectable marker cassette. ES cells that had successfully undergone Cre recombination and no longer retained the cassette but did retain the loxP-flanked exon 3 were injected into recipient blastocysts. The resulting chimeric animals were crossed to other mutant strains. Upon arrival at The Jackson Laboratory the mice were crossed to C57BL/6J at least once to remove the other mutant allele and to establish the colony.

Control Information

  Control
   101043 B6129SF1/J (approximate)
 
  Considerations for Choosing Controls

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.
Insulin-Like Growth Factor I, Resistance to   (IGF1R)
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.

Igf1rtm2Arge/Igf1r+ Tg(Tek-cre)1Ywa/0

        B6.Cg-Igf1rtm2Arge Tg(Tek-cre)1Ywa   (conditional)
  • cardiovascular system phenotype
  • abnormal vascular endothelial cell physiology
    • blunted endothelial regeneration after arterial injury compared with wild-type cells   (MGI Ref ID J:208523)
  • abnormal vascular wound healing
    • blunted endothelial regeneration after arterial injury compared with wild-type cells   (MGI Ref ID J:208523)
  • homeostasis/metabolism phenotype
  • abnormal vascular wound healing
    • blunted endothelial regeneration after arterial injury compared with wild-type cells   (MGI Ref ID J:208523)

Igf1rtm2Arge/Igf1rtm2Arge Tg(BGLAP-cre)1Clem/0

        involves: 129 * FVB/N   (conditional)
  • skeleton phenotype
  • abnormal skeleton morphology
    • phenotype is quantitatively similar, but less pronounced in males compared to females   (MGI Ref ID J:80190)
    • abnormal neurocranium morphology
      • calvarial cortical thickness is reduced to ~80% of control   (MGI Ref ID J:80190)
    • abnormal trabecular bone morphology
      • trabecular separation is increased by 44% compared to controls   (MGI Ref ID J:80190)
      • in secondary spongiosa of distal femur in 6-week old females, trabecular separation is increased; trabecular connectivity is 35% lower than normal   (MGI Ref ID J:80190)
      • decreased bone trabecula number
        • trabecular number is decreased by 29%   (MGI Ref ID J:80190)
      • decreased trabecular bone thickness
        • trabecular thickness is decreased by 25%   (MGI Ref ID J:80190)
      • decreased trabecular bone volume
        • trabecular bone volume is decreased by 46%   (MGI Ref ID J:80190)
        • in secondary spongiosa of distal femur in 6-week old females, cancellous bone volume is ~24% lower than controls   (MGI Ref ID J:80190)
    • decreased osteoblast cell number
      • significant reduction in number (67-69%) per bone perimeter is seen relative to controls   (MGI Ref ID J:80190)
    • decreased osteoclast cell number
      • significant reduction in number (67-69%) per bone perimeter is seen relative to controls   (MGI Ref ID J:80190)
  • abnormal skeleton physiology
    • phenotype is quantitatively similar, but less pronounced in males compared to females   (MGI Ref ID J:80190)
    • abnormal bone ossification
      • in 3-week old females, epiphyseal bone formation rate is reduced to ~42% of control mice   (MGI Ref ID J:80190)
      • abnormal bone mineralization
        • mineral apposition rate is impaired in 6-week old females   (MGI Ref ID J:80190)
    • abnormal osteoblast physiology
      • increase in osteoclast erosion surface accompanies increase in osteoid   (MGI Ref ID J:80190)
    • abnormal osteoclast physiology
      • amount of osteoid is significantly increased in female mutants at 6-weeks   (MGI Ref ID J:80190)
  • craniofacial phenotype
  • abnormal neurocranium morphology
    • calvarial cortical thickness is reduced to ~80% of control   (MGI Ref ID J:80190)
  • immune system phenotype
  • abnormal osteoclast physiology
    • amount of osteoid is significantly increased in female mutants at 6-weeks   (MGI Ref ID J:80190)
  • decreased osteoclast cell number
    • significant reduction in number (67-69%) per bone perimeter is seen relative to controls   (MGI Ref ID J:80190)
  • hematopoietic system phenotype
  • abnormal osteoclast physiology
    • amount of osteoid is significantly increased in female mutants at 6-weeks   (MGI Ref ID J:80190)
  • decreased osteoclast cell number
    • significant reduction in number (67-69%) per bone perimeter is seen relative to controls   (MGI Ref ID J:80190)
View Research Applications

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

Research Tools
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Igf1rtm2Arge
Allele Name targeted mutation 2, Argiris Efstratiadis
Allele Type Targeted (Conditional ready (e.g. floxed), No functional change)
Common Name(s) IGF1RLox; Igf1rc;
Mutation Made By Shouhong Xuan,   Columbia University
Strain of Origin129/SvEv
Gene Symbol and Name Igf1r, insulin-like growth factor I receptor
Chromosome 7
Gene Common Name(s) A330103N21Rik; CD221; IGF-1R; IGFIR; IGFIRC; IGFR; JTK13; RIKEN cDNA A330103N21 gene; hydrops fetalis; hyft; line 186;
Molecular Note Exon 3 was flanked by a floxed neo cassette in intron 2 and a single loxP site in intron 3. [MGI Ref ID J:60711]

Genotyping

Genotyping Information

Genotyping Protocols

Igf1rtm2Arge, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Dietrich P; Dragatsis I; Xuan S; Zeitlin S; Efstratiadis A. 2000. Conditional mutagenesis in mice with heat shock promoter-driven cre transgenes. Mamm Genome 11(3):196-205. [PubMed: 10723724]  [MGI Ref ID J:60711]

Additional References

Igf1rtm2Arge related

Abbas A; Imrie H; Viswambharan H; Sukumar P; Rajwani A; Cubbon RM; Gage M; Smith J; Galloway S; Yuldeshava N; Kahn M; Xuan S; Grant PJ; Channon KM; Beech DJ; Wheatcroft SB; Kearney MT. 2011. The insulin-like growth factor-1 receptor is a negative regulator of nitric oxide bioavailability and insulin sensitivity in the endothelium. Diabetes 60(8):2169-78. [PubMed: 21677284]  [MGI Ref ID J:186813]

DiGirolamo DJ; Mukherjee A; Fulzele K; Gan Y; Cao X; Frank SJ; Clemens TL. 2007. Mode of growth hormone action in osteoblasts. J Biol Chem 282(43):31666-74. [PubMed: 17698843]  [MGI Ref ID J:126795]

Gan Y; Paterson AJ; Zhang Y; Jiang J; Frank SJ. 2014. Functional collaboration of insulin-like growth factor-1 receptor (IGF-1R), but not insulin receptor (IR), with acute GH signaling in mouse calvarial cells. Endocrinology 155(3):1000-9. [PubMed: 24302626]  [MGI Ref ID J:208707]

Gan Y; Zhang Y; Digirolamo DJ; Jiang J; Wang X; Cao X; Zinn KR; Carbone DP; Clemens TL; Frank SJ. 2010. Deletion of IGF-I Receptor (IGF-IR) in Primary Osteoblasts Reduces GH-Induced STAT5 Signaling. Mol Endocrinol 24(3):644-56. [PubMed: 20133448]  [MGI Ref ID J:157582]

Imrie H; Viswambharan H; Sukumar P; Abbas A; Cubbon RM; Yuldasheva N; Gage M; Smith J; Galloway S; Skromna A; Rashid ST; Futers TS; Xuan S; Gatenby VK; Grant PJ; Channon KM; Beech DJ; Wheatcroft SB; Kearney MT. 2012. Novel role of the IGF-1 receptor in endothelial function and repair: studies in endothelium-targeted IGF-1 receptor transgenic mice. Diabetes 61(9):2359-68. [PubMed: 22733797]  [MGI Ref ID J:208523]

Klinakis A; Szabolcs M; Chen G; Xuan S; Hibshoosh H; Efstratiadis A. 2009. Igf1r as a therapeutic target in a mouse model of basal-like breast cancer. Proc Natl Acad Sci U S A 106(7):2359-64. [PubMed: 19174523]  [MGI Ref ID J:146290]

Long F; Joeng KS; Xuan S; Efstratiadis A; McMahon AP. 2006. Independent regulation of skeletal growth by Ihh and IGF signaling. Dev Biol 298(1):327-33. [PubMed: 16905129]  [MGI Ref ID J:119575]

Mason JL; Xuan S; Dragatsis I; Efstratiadis A; Goldman JE. 2003. Insulin-like growth factor (IGF) signaling through type 1 IGF receptor plays an important role in remyelination. J Neurosci 23(20):7710-8. [PubMed: 12930811]  [MGI Ref ID J:88198]

Niu T; Rosen CJ. 2005. The insulin-like growth factor-I gene and osteoporosis: a critical appraisal. Gene 361:38-56. [PubMed: 16183214]  [MGI Ref ID J:102683]

Okano T; Xuan S; Kelley MW. 2011. Insulin-like growth factor signaling regulates the timing of sensory cell differentiation in the mouse cochlea. J Neurosci 31(49):18104-18. [PubMed: 22159122]  [MGI Ref ID J:178908]

Pitetti JL; Calvel P; Romero Y; Conne B; Truong V; Papaioannou MD; Schaad O; Docquier M; Herrera PL; Wilhelm D; Nef S. 2013. Insulin and IGF1 receptors are essential for XX and XY gonadal differentiation and adrenal development in mice. PLoS Genet 9(1):e1003160. [PubMed: 23300479]  [MGI Ref ID J:197599]

Rajwani A; Ezzat V; Smith J; Yuldasheva NY; Duncan ER; Gage M; Cubbon RM; Kahn MB; Imrie H; Abbas A; Viswambharan H; Aziz A; Sukumar P; Vidal-Puig A; Sethi JK; Xuan S; Shah AM; Grant PJ; Porter KE; Kearney MT; Wheatcroft SB. 2012. Increasing circulating IGFBP1 levels improves insulin sensitivity, promotes nitric oxide production, lowers blood pressure, and protects against atherosclerosis. Diabetes 61(4):915-24. [PubMed: 22357965]  [MGI Ref ID J:196733]

Wang Y; Nishida S; Boudignon BM; Burghardt A; Elalieh HZ; Hamilton MM; Majumdar S; Halloran BP; Clemens TL; Bikle DD. 2007. IGF-I receptor is required for the anabolic actions of parathyroid hormone on bone. J Bone Miner Res 22(9):1329-37. [PubMed: 17539737]  [MGI Ref ID J:141364]

Xian L; Wu X; Pang L; Lou M; Rosen CJ; Qiu T; Crane J; Frassica F; Zhang L; Rodriguez JP; Xiaofeng Jia; Shoshana Yakar; Shouhong Xuan; Argiris Efstratiadis; Mei Wan; Xu Cao. 2012. Matrix IGF-1 maintains bone mass by activation of mTOR in mesenchymal stem cells. Nat Med 18(7):1095-101. [PubMed: 22729283]  [MGI Ref ID J:197585]

Xuan S; Kitamura T; Nakae J; Politi K; Kido Y; Fisher PE; Morroni M; Cinti S; White MF; Herrera PL; Accili D; Efstratiadis A. 2002. Defective insulin secretion in pancreatic beta cells lacking type 1 IGF receptor. J Clin Invest 110(7):1011-9. [PubMed: 12370279]  [MGI Ref ID J:79805]

Xuan S; Szabolcs M; Cinti F; Perincheri S; Accili D; Efstratiadis A. 2010. Genetic analysis of type-1 insulin-like growth factor receptor signaling through insulin receptor substrate-1 and -2 in pancreatic beta cells. J Biol Chem 285(52):41044-50. [PubMed: 20947509]  [MGI Ref ID J:167586]

Zeger M; Popken G; Zhang J; Xuan S; Lu QR; Schwab MH; Nave KA; Rowitch D; D'Ercole AJ; Ye P. 2007. Insulin-like growth factor type 1 receptor signaling in the cells of oligodendrocyte lineage is required for normal in vivo oligodendrocyte development and myelination. Glia 55(4):400-11. [PubMed: 17186502]  [MGI Ref ID J:156105]

Zhang M; Xuan S; Bouxsein ML; von Stechow D; Akeno N; Faugere MC; Malluche H; Zhao G; Rosen CJ; Efstratiadis A; Clemens TL. 2002. Osteoblast-specific knockout of the insulin-like growth factor (IGF) receptor gene reveals an essential role of IGF signaling in bone matrix mineralization. J Biol Chem 277(46):44005-12. [PubMed: 12215457]  [MGI Ref ID J:80190]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX10

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice can be bred as homozygotes.
Mating SystemHomozygote x Homozygote         (Female x Male)   04-JUN-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 $239.00Female or MaleHomozygous for Igf1rtm2Arge  
Price per Pair (US dollars $)Pair Genotype
$478.00Homozygous for Igf1rtm2Arge x Homozygous for Igf1rtm2Arge  

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 $310.70Female or MaleHomozygous for Igf1rtm2Arge  
Price per Pair (US dollars $)Pair Genotype
$621.40Homozygous for Igf1rtm2Arge x Homozygous for Igf1rtm2Arge  

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
   101043 B6129SF1/J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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.
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