Strain Name:

FVB-Tg(Ckm-IGF1R*K1003R)1Dlr/J

Stock Number:

016618

Order this mouse

Availability:

Cryopreserved - Ready for recovery

MKR transgenic mice have the murine Ckm promoter directing expression of the human IGF-1R gene containing the K1003R mutation. These mice may be useful for studying insulin signaling and Type 2 Diabetes.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Coisogenic; Mutant Strain; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
Generation+pN1
Generation Definitions
 
Donating InvestigatorDr. Derek LeRoith,   Mount Sinai School of Medicine

Description
MKR transgenic mice have the murine creatine kinase, muscle (Ckm) promoter directing expression of the human insulin-like growth factor I receptor (IGF-1R) gene containing the K1003R mutation. Homozygous MKR mice are viable and fertile. IGF-1R is a tyrosine kinase transmembrane receptor dimer which mediated cell signaling through IGF binding and promotes cell survival and cell proliferation. The K1003R mutation inactivates the ATP binding site of the receptor. These transgenic mice have ~12 copies of the transgene, and exhibit a 10 fold increase in expression in skeletal muscle, with weak expression in cardiac muscle. Expression of the mutant receptor results in the formation of hybrid receptors with endogenous IGF-1R and insulin receptors, leading to a decrease in glucose uptake, insulin resistance, beta cell dysfunctions, and rapid development of diabetes. These mice exhibit 20% reduction in body weight during the first month of life, and continue to have a 10% reduction in body weight throughout life compared to wildtype. These mice may be useful for studying insulin signaling and Type 2 Diabetes.

Development
The MKR transgene was designed with the human insulin-like growth factor I receptor (IGF-1R) gene driven by a murine creatine kinase, muscle (Ckm) promoter. The point mutation K1003R was introduced, resulting in a dominant negative IGF-1R. The transgene was microinjected into fertilized FVB/N oocytes, and founder mice were bred to FVB/N mice. Upon arrival at The Jackson Laboratory, transgenic mice were bred to FVB/NJ inbred mice (Stock No. 001800) for at least one generation.

Control Information

  Control
   Noncarrier
   001800 FVB/NJ (approximate)
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying other alleles of Ckm     (11 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.
Diabetes Mellitus, Noninsulin-Dependent; NIDDM
- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. 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

Tg(Ckm-IGF1R*K1003R)1Dlr/0

        FVB/N-Tg(Ckm-IGF1R*K1003R)1Dlr
  • homeostasis/metabolism phenotype
  • abnormal glucose homeostasis
    • total body glucose disposal, glycolysis, and glycogen synthesis are reduced compared to in wild-type mice   (MGI Ref ID J:71205)
    • abnormal glycogen homeostasis
      • glycogen synthesis is reduced compared to in wild-type mice   (MGI Ref ID J:71205)
    • impaired glucose tolerance
      • at 7 to 12 weeks   (MGI Ref ID J:71205)
    • increased circulating glucose level   (MGI Ref ID J:71205)
    • increased circulating insulin level
      • at 2 weeks of age   (MGI Ref ID J:71205)
    • insulin resistance   (MGI Ref ID J:71205)
  • abnormal response/metabolism to endogenous compounds
    • following stimulation with IGF-I, muscle fails to exhibit an increase in glucose uptake unlike in similarly treated wild-type muscle   (MGI Ref ID J:71205)
  • increased circulating free fatty acid level
    • 2-fold at 3 to 4 weeks of age   (MGI Ref ID J:71205)
  • increased circulating triglyceride level
    • 2-fold at 3 to 4 weeks of age   (MGI Ref ID J:71205)
  • increased liver triglyceride level   (MGI Ref ID J:71205)
  • muscle phenotype
  • abnormal muscle cell glucose uptake
    • insulin stimulated glucose uptake is 1.5-fold compared to 5-fold in wild-type mice   (MGI Ref ID J:71205)
    • following stimulation with IGF-I, muscle fails to exhibit an increase in glucose uptake unlike in similarly treated wild-type muscle   (MGI Ref ID J:71205)
  • endocrine/exocrine gland phenotype
  • pancreatic islet hyperplasia   (MGI Ref ID J:71205)
  • cellular phenotype
  • impaired cellular glucose import
    • glucose transport activity in skeletal muscle and brown adipose tissue is reduced 50% compared to in wild-type cells   (MGI Ref ID J:71205)
  • growth/size/body phenotype
  • decreased body weight
    • 20% from birth to 4 weeks of age and 10% from 4 weeks of age through adulthood   (MGI Ref ID J:71205)
  • postnatal growth retardation
    • mice exhibit modest growth retardation from birth to 4 weeks of age and a smaller reduction in growth from 4 weeks of age through adulthood compared to in wild-type mice   (MGI Ref ID J:71205)
  • liver/biliary system phenotype
  • increased liver triglyceride level   (MGI Ref ID J:71205)
View Research Applications

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

Cell Biology Research
Signal Transduction

Diabetes and Obesity Research
Insulin Receptors and Growth Factors
Insulin Resistance
Type 2 Diabetes (NIDDM)

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tg(Ckm-IGF1R*K1003R)1Dlr
Allele Name transgene marker 1, Derek LeRoith
Allele Type Transgenic (Dominant negative, Inserted expressed sequence)
Common Name(s) MCK-KR-hIGF-IR; MKR;
Mutation Made ByDr. Derek LeRoith,   Mount Sinai School of Medicine
Strain of OriginFVB/N
Expressed Gene IGF1R, insulin-like growth factor 1 receptor, human
Promoter Ckm, creatine kinase, muscle, mouse, laboratory
Molecular Note The promoter, enhancer 1, exon 1, first intron/enchancer 2, and first 16 base pairs of exon 2 were used to drive muscle-specific expression of a dominant-negative human gene with nucleotide substitutions that result in the amino acid substitution of arginine for lysine at position 1003 (K1003R). Five lines were created with around 12 copies of the transgene. No line names were given. [MGI Ref ID J:71205]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(Ckm-IGF1R*K1003R)1Dlr, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Fernandez AM; Kim JK; Yakar S; Dupont J; Hernandez-Sanchez C; Castle AL; Filmore J; Shulman GI; Le Roith D. 2001. Functional inactivation of the IGF-I and insulin receptors in skeletal muscle causes type 2 diabetes. Genes Dev 15(15):1926-34. [PubMed: 11485987]  [MGI Ref ID J:71205]

Additional References

Tg(Ckm-IGF1R*K1003R)1Dlr related

Asghar Z; Yau D; Chan F; Leroith D; Chan CB; Wheeler MB. 2006. Insulin resistance causes increased beta-cell mass but defective glucose-stimulated insulin secretion in a murine model of type 2 diabetes. Diabetologia 49(1):90-99. [PubMed: 16362284]  [MGI Ref ID J:105802]

Fernandez AM; Dupont J; Farrar RP; Lee S; Stannard B; Le Roith D. 2002. Muscle-specific inactivation of the IGF-I receptor induces compensatory hyperplasia in skeletal muscle. J Clin Invest 109(3):347-55. [PubMed: 11827994]  [MGI Ref ID J:128672]

Fierz Y; Novosyadlyy R; Vijayakumar A; Yakar S; LeRoith D. 2010. Insulin-sensitizing therapy attenuates type 2 diabetes-mediated mammary tumor progression. Diabetes 59(3):686-93. [PubMed: 19959755]  [MGI Ref ID J:164155]

Gallagher EJ; Alikhani N; Tobin-Hess A; Blank J; Buffin NJ; Zelenko Z; Tennagels N; Werner U; LeRoith D. 2013. Insulin receptor phosphorylation by endogenous insulin or the insulin analog AspB10 promotes mammary tumor growth independent of the IGF-I receptor. Diabetes 62(10):3553-60. [PubMed: 23835331]  [MGI Ref ID J:208949]

Heron-Milhavet L; Haluzik M; Yakar S; Gavrilova O; Pack S; Jou WC; Ibrahimi A; Kim H; Hunt D; Yau D; Asghar Z; Joseph J; Wheeler MB; Abumrad NA; LeRoith D. 2004. Muscle-specific overexpression of CD36 reverses the insulin resistance and diabetes of MKR mice. Endocrinology 145(10):4667-76. [PubMed: 15231693]  [MGI Ref ID J:108732]

Kalista S; Schakman O; Gilson H; Lause P; Demeulder B; Bertrand L; Pende M; Thissen JP. 2012. The type 1 insulin-like growth factor receptor (IGF-IR) pathway is mandatory for the follistatin-induced skeletal muscle hypertrophy. Endocrinology 153(1):241-53. [PubMed: 22087027]  [MGI Ref ID J:181804]

Kawashima Y; Chen J; Sun H; Lann D; Hajjar RJ; Yakar S; Leroith D. 2009. Apolipoprotein E deficiency abrogates insulin resistance in a mouse model of type 2 diabetes mellitus. Diabetologia 52(7):1434-41. [PubMed: 19436992]  [MGI Ref ID J:166108]

Kawashima Y; Fritton JC; Yakar S; Epstein S; Schaffler MB; Jepsen KJ; LeRoith D. 2009. Type 2 diabetic mice demonstrate slender long bones with increased fragility secondary to increased osteoclastogenesis. Bone 44(4):648-55. [PubMed: 19150422]  [MGI Ref ID J:147176]

Kim H; Haluzik M; Asghar Z; Yau D; Joseph JW; Fernandez AM; Reitman ML; Yakar S; Stannard B; Heron-Milhavet L; Wheeler MB; LeRoith D. 2003. Peroxisome proliferator-activated receptor-alpha agonist treatment in a transgenic model of type 2 diabetes reverses the lipotoxic state and improves glucose homeostasis. Diabetes 52(7):1770-8. [PubMed: 12829645]  [MGI Ref ID J:84294]

Lu H; Koshkin V; Allister EM; Gyulkhandanyan AV; Wheeler MB. 2010. Molecular and metabolic evidence for mitochondrial defects associated with beta-cell dysfunction in a mouse model of type 2 diabetes. Diabetes 59(2):448-59. [PubMed: 19903739]  [MGI Ref ID J:164163]

Mallipattu SK; Gallagher EJ; LeRoith D; Liu R; Mehrotra A; Horne SJ; Chuang PY; Yang VW; He JC. 2014. Diabetic nephropathy in a nonobese mouse model of type 2 diabetes mellitus. Am J Physiol Renal Physiol 306(9):F1008-17. [PubMed: 24598803]  [MGI Ref ID J:210518]

Novosyadlyy R; Lann DE; Vijayakumar A; Rowzee A; Lazzarino DA; Fierz Y; Carboni JM; Gottardis MM; Pennisi PA; Molinolo AA; Kurshan N; Mejia W; Santopietro S; Yakar S; Wood TL; LeRoith D. 2010. Insulin-mediated acceleration of breast cancer development and progression in a nonobese model of type 2 diabetes. Cancer Res 70(2):741-51. [PubMed: 20068149]  [MGI Ref ID J:156752]

Pennisi P; Gavrilova O; Setser-Portas J; Jou W; Santopietro S; Clemmons D; Yakar S; LeRoith D. 2006. Recombinant human insulin-like growth factor-I treatment inhibits gluconeogenesis in a transgenic mouse model of type 2 diabetes mellitus. Endocrinology 147(6):2619-30. [PubMed: 16513827]  [MGI Ref ID J:109445]

Rostoker R; Bitton-Worms K; Caspi A; Shen-Orr Z; LeRoith D. 2013. Investigating new therapeutic strategies targeting hyperinsulinemia's mitogenic effects in a female mouse breast cancer model. Endocrinology 154(5):1701-10. [PubMed: 23515289]  [MGI Ref ID J:197917]

Spangenburg EE; Le Roith D; Ward CW; Bodine SC. 2008. A functional insulin-like growth factor receptor is not necessary for load-induced skeletal muscle hypertrophy. J Physiol 586(1):283-91. [PubMed: 17974583]  [MGI Ref ID J:176414]

Toyoshima Y; Gavrilova O; Yakar S; Jou W; Pack S; Asghar Z; Wheeler MB; LeRoith D. 2005. Leptin improves insulin resistance and hyperglycemia in a mouse model of type 2 diabetes. Endocrinology 146(9):4024-35. [PubMed: 15947005]  [MGI Ref ID J:129800]

Vaitheesvaran B; LeRoith D; Kurland IJ. 2010. MKR mice have increased dynamic glucose disposal despite metabolic inflexibility, and hepatic and peripheral insulin insensitivity. Diabetologia 53(10):2224-32. [PubMed: 20577711]  [MGI Ref ID J:165163]

Vijayakumar A; Buffin NJ; Gallagher EJ; Blank J; Wu Y; Yakar S; LeRoith D. 2013. Deletion of growth hormone receptors in postnatal skeletal muscle of male mice does not alter muscle mass and response to pathological injury. Endocrinology 154(10):3776-83. [PubMed: 23861377]  [MGI Ref ID J:203293]

Witkowski S; Lovering RM; Spangenburg EE. 2010. High-frequency electrically stimulated skeletal muscle contractions increase p70s6k phosphorylation independent of known IGF-I sensitive signaling pathways. FEBS Lett 584(13):2891-5. [PubMed: 20466004]  [MGI Ref ID J:161316]

Zhao H; Yakar S; Gavrilova O; Sun H; Zhang Y; Kim H; Setser J; Jou W; Leroith D. 2004. Phloridzin improves hyperglycemia but not hepatic insulin resistance in a transgenic mouse model of type 2 diabetes. Diabetes 53(11):2901-9. [PubMed: 15504971]  [MGI Ref ID J:93184]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, hemizygous mice may be bred with wildtype (non-carrier) mice from the colony or to FVB/NJ inbred mice (Stock No. 001800).

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


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

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2140.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2782.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Noncarrier
   001800 FVB/NJ (approximate)
 
  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.


(6.8)