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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
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Description
Strain Information
Former Names NOD.FVB-Tg(INS-MT2A, Tyr)1Pne/PneJ (Changed: 15-DEC-04 ) Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain NOD Donor Strain FVB H2 Haplotype g7 Donating Investigator Paul Epstein, University of Louisville Description
Transgenic mice are viable, fertile, and normal in size, display accelerated spontaneous diabetes onset, especially in males, and have coat color pigmentation. Immunohistochemical staining with metallothionein specific antibodies confirms pancreatic islet cell specific expression of the INS-MT2A transgene. There is a 40-fold increase in metallothionein activity in transgenic islets when compared to wild-type controls. 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 in ROS florescence in wild-type islets, but a very small increase in transgenic islets. Transgenic beta cells are diabetes resistant to diabetes when treated with streptozotocin. Transgenic beta cells generate less ROS fluorescence when treated with hydrogen peroxide, superoxide or peroxynitrite and islet transplantation is improved on he FVB background (Li et al 2004). But surprisingly diabetes onset is greatly accelerated in cyclophosphamide treated transgenic mice when compared with NOD controls. Histology indicates that transgenic mice treated 6 days prior to analysis have significant islet atrophy(apoptosis). This wave of apoptosis precedes hyperglycemia and an eight-fold decline in pancreatic insulin. In vivo and in vitro findings indicate reduced activation of the IRS/Akt/PDX1 pathway. This model provides a tool for looking at the role of oxidative stress in diabetes.Development
NOD.FVB-Tg(INS-MT2A,Tyr)1Pne/PneJ expresses the full-length human metallothionein IIA gene controlled by the human insulin promoter and first intron (Chen et, al., 2001). In addition, these mice express tyrosinase under the control of the tyrosinase promoter, commonly referred to as TyBs or tyrosinase minigene (Chen et, al., 2001, Overbeek, et al., 1991). These transgenes were first co-inserted by Chen et, al., (2001) 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 7 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(INS-MT2A,Tyr)1Pne/PneJ at generation N7F8.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001976 NOD/ShiLtJ | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of INS
005113 NOD.FVB-Tg(INS-SOD2)3Pne/PneJ View Strains carrying other alleles of INS (1 strain)
Additional Web Information
Congenic Nomenclature
Genetic Quality Control Annual Report
Phenotype
Phenotype Information
assigned by genotype
Tg(INS-MT2A,Tyr)1Pne/0
NOD.FVB-Tg(INS-MT2A,Tyr)1Pne
- homeostasis/metabolism phenotype
- decreased 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 93% of transgenic mice are diabetic compared with 7% of treated controls
- transgenic mice on the FVB background do not develop diabetes with the same regimen of CYP treatment as the NOD transgenic mice
- transgenic mice exhibit greater resistance to induced diabetes after treatment with streptozotocin compared with NOD controls
- endocrine/exocrine gland phenotype
- abnormal islet of Langerhans morphology (MGI Ref ID J:108415)
- 8 days after CYP treatment significantly more islets of transgenic NOD mice appear small and disrupted compared to treated NOD controls; percentages of damaged areas (Caspase-3 positive) in islets are 11.7 and 5.5% in transgenic NOD and control NOD mice respectively
- 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 36% of original level after 8 days compared to 76% in control NOD mice
- digestive/alimentary phenotype
- abnormal islet of Langerhans morphology (MGI Ref ID J:108415)
- 8 days after CYP treatment significantly more islets of transgenic NOD mice appear small and disrupted compared to treated NOD controls; percentages of damaged areas (Caspase-3 positive) in islets are 11.7 and 5.5% in transgenic NOD and control NOD mice respectively
- 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 36% 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(INS-MT2A,Tyr)1Pne | ||
|---|---|---|---|
| Allele Name | transgene insertion 1, Paul N Epstein | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | HMT-1; | ||
| Mutation Made By | Paul Epstein, University of Louisville | ||
| Strain of Origin | FVB | ||
| Expressed Gene | Tyr, tyrosinase, mouse, laboratory | ||
| Expressed Gene | MT2A, metallothionein 2A, human | ||
| Promoter | INS, insulin, human | ||
| Molecular Note | This transgene expresses the full length human metallothionein II gene under the control of the human insulin promoter and first intron. A second transgene that expresses tyrosinase under the control of the tyrosinase promoter was coinjected with the first transgene, and appears to cosegregate. [MGI Ref ID J:90564] | ||
Genotyping
Genotyping Information
This strain will not have a genotyping protocol or one is not currently available.
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Chen H; Carlson EC; Pellet L; Moritz JT; Epstein PN. 2001. Overexpression of metallothionein in pancreatic beta-cells reduces streptozotocin-induced DNA damage and diabetes. Diabetes 50(9):2040-6. [PubMed: 11522669] [MGI Ref ID J:90564]
Additional References
Tg(INS-MT2A,Tyr)1Pne relatedChen H; Li X; Epstein PN. 2005. MnSOD and catalase transgenes demonstrate that protection of islets from oxidative stress does not alter cytokine toxicity. Diabetes 54(5):1437-46. [PubMed: 15855331] [MGI Ref ID J:97839]
Li 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]
Li X; Chen H; Epstein PN. 2004. Metallothionein protects islets from hypoxia and extends islet graft survival by scavenging most kinds of reactive oxygen species. J Biol Chem 279(1):765-71. [PubMed: 14576162] [MGI Ref ID J:95089]
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 |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00 Cryopreserved Embryos Fee $1600.00
Additional Supply Details
| Pricing for International shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00 Cryopreserved Embryos Fee $2080.00
Additional Supply Details
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Supply Details
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. 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. | ||
General Terms and Conditions
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