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- Description
- Phenotype
- Genes & alleles
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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
Former Names NOD.FVB-Tg(Ins1-Cat, Tyr)25Pne/PneJ (Changed: 15-DEC-04 ) Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Background Strain NOD Donor Strain FVB H2 Haplotype g7 Generation N10F4+N1p (03-APR-05) Donating Investigator Paul Epstein, University of Louisville Description
Transgenic mice are viable, fertile, and normal in size, display accelerated spontaneous diabetes onset in males, and have coat color pigmentation. Northern blot analysis and immunohistochemistry confirm pancreatic islet specific expression of the Ins1-Cat transgene. There is a 50-fold increase in catalase activity in transgenic islets when compared to wild-type controls, which approximates catalase activity normally found in the liver. Insulin and DNA content, insulin staining and islet morphology in transgenic animals is essentially the same as in wild-type controls.Transgenic islets have a similar reactive oxygen species (ROS) level as wild-type controls in normal media. However, after exposure to cytokines there is a significant increase of ROS florescence in control islets, but much smaller increase in transgenic islets. Transgenic mice are resistant to diabetes when treated with streptozotocin or alloxan. Transgenic beta cells generate less ROS fluorescence when treated with hydrogen peroxide, superoxide or peroxynitrite, but surprisingly cyclophosphamide accelerates diabetes onset in transgenic mice.
This model provides a tool for looking at the role of oxidative stress in diabetes.
Development
NOD.FVB-Tg(Ins1-Cat, Tyr)25Pne/PneJ expresses the full-length rat catalase cDNA under the control of the rat insulin 1 promoter. In addition, these mice express tyrosinase under the control of the tyrosinase promoter, commonly referred to as TyBs or tyrosinase minigene (Xu et al, 1999, Overbeek et al., 1991). These transgenes were first co-inserted by Xu et al., (1999) into FVB oocytes. Transgenic founders carrying both genes were mated to FVB and found to co-segregate. This strain was maintained by Epstein et al., and backcrossed to NOD for 8 generations. A genome wide scan confirmed that all known Idd markers were homozygous for the NOD allele. In 2004, The Jackson Laboratory received NOD.FVB-Tg(Ins1-Cat,Tyr)25Pne/PneJ at generation N8F7.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001976 NOD/ShiLtJ | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Ins1
005282 NOD/ShiLtJ-Tg(Ins1-EGFP/GH1)14Hara/HaraJ View Strains carrying other alleles of Ins1 (1 strain)
Additional Web Information
Genetic Quality Control Annual Report
Phenotype
Phenotype Information
assigned by genotype
Tg(Ins1-Cat,Tyr)25Pne/0
NOD.FVB-Tg(Ins1-Cat,Tyr)25Pne
- homeostasis/metabolism phenotype
- increased physiological sensitivity to xenobiotics (MGI Ref ID J:108415)
- treatment of transgenic NOD mice with cyclophosphamide (CYP) accelerated NOD diabetes; 20 days after injection of CYP 63% of transgenic mice are diabetic compared with 7% of treated controls
- immune system phenotype
- increased susceptibility to autoimmune diabetes (MGI Ref ID J:108415)
- transgenic NOD male mice display a significant acceleration of the onset of spontaneous diabetes (over 85% at 200 days of age) compared to NOD controls (30-40% of male NOD mice)
- endocrine/exocrine gland phenotype
- abnormal pancreatic islet morphology (MGI Ref ID J:108415)
- cultured islets of transgenic NOD mice are more sensitive to a mix of cytokines (Il-beta, Tnfa and Ifng) than NOD control islets as revealed by Caspase-3 activity
- decreased pancreatic beta cell number (MGI Ref ID J:108415)
- beta cell damage is significantly increased in transgenic mice after CYP injection compared to controls; pancreatic insulin content is only 22% of original level after 8 days compared to 76% in control NOD mice
- digestive/alimentary phenotype
- abnormal pancreatic islet morphology (MGI Ref ID J:108415)
- cultured islets of transgenic NOD mice are more sensitive to a mix of cytokines (Il-beta, Tnfa and Ifng) than NOD control islets as revealed by Caspase-3 activity
- decreased pancreatic beta cell number (MGI Ref ID J:108415)
- beta cell damage is significantly increased in transgenic mice after CYP injection compared to controls; pancreatic insulin content is only 22% of original level after 8 days compared to 76% in control NOD mice
This mouse can be used to support research in many areas including:
Diabetes and Obesity Research
Type 1 Diabetes (IDDM) Analysis Strains
NOD Transgenics
Immunology and Inflammation Research
Autoimmunity
Type 1 Diabetes
Research Tools
Apoptosis Research
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(Ins1-Cat,Tyr)25Pne | ||
|---|---|---|---|
| Allele Name | transgene insertion 25, Paul N Epstein | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | RipCat; | ||
| Mutation Made By | Paul Epstein, University of Louisville | ||
| Strain of Origin | FVB | ||
| Expressed Gene | Cat, catalase, rat | ||
| Expressed Gene | Tyr, tyrosinase, mouse, laboratory | ||
| Promoter | Ins1, insulin 1, rat | ||
| Molecular Note | The symbol represents a double transgene. In one transgene, a rat insulin I promoter drives the expression of a rat catalase cDNA. Northern blot analysis and immunohistochemistry detected expression of this transgene in pancreatic beta cells. A second transgene that expresses tyrosinase under control of the tyrosinase promoter was coinjected with the first transgene, and apparently cosegregated. [MGI Ref ID J:59725] | ||
Genotyping
Genotyping Information
This strain will not have a genotyping protocol or one is not currently available.
Helpful Links
Genotyping resources and troubleshooting
References
References
Selected Reference(s)
Xu B; Moritz JT; Epstein PN. 1999. Overexpression of catalase provides partial protection to transgenic mouse beta cells. Free Radic Biol Med 27(7-8):830-7. [PubMed: 10515587] [MGI Ref ID J:59725]
Additional References
Tg(Ins1-Cat,Tyr)25Pne relatedLi X; Chen H; Epstein PN. 2006. Metallothionein and Catalase Sensitize to Diabetes in Nonobese Diabetic Mice: Reactive Oxygen Species May Have a Protective Role in Pancreatic {beta}-Cells. Diabetes 55(6):1592-604. [PubMed: 16731821] [MGI Ref ID J:108415]
Rowen L; Qin S; Madan A; Abbasi N; James R; Dickoff R; Shaffer T; Ratcliffe A; Loretz C; Lasky S; Hood L. 1999. Mus musculus casein kinase 2 beta subunit (gMCK2) gene, partial cds; BAT4, NG20 (NG20), BAT3, BAT2, AIF-1, B144, lymphotoxin beta, TNF, and TNF beta genes, complete cds; IKBL gene, partial cds; and unknown gene GenBank Submission :AF109719. [MGI Ref ID J:59275]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
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Animals Provided
Price (US dollars $) Cryorecovery Fee $1900.00 Cryopreserved Embryos $1600.00 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.
Additional Supply Details
| Pricing for International shipping destinations |
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Animals Provided
Price (US dollars $) Cryorecovery Fee $2470.00 Cryopreserved Embryos $2080.00 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.
Additional Supply Details
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Supply Details
| Standard Supply | Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001976 NOD/ShiLtJ | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - 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.Ordering and Purchasing Information
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