Strain Name: |
NOD.FVB-Tg(INS-MT2A,Tyr)1Pne/PneJ |
|---|---|
Stock Number: |
005115 |
Availability: | Repository-Cryopreserved |
General Terms and Conditions |
| Former Name |
NOD.FVB-Tg(INS-MT2A, Tyr)1Pne/PneJ (Changed: 15-DEC-04
) |
| Genes & Alleles | INS; MT2A; Tyr; Tg(INS-MT2A,Tyr)1Pne; |
Product Information
Strain Details
Type JAX® GEMM® Strain - Congenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Mutant Strain Type JAX® GEMM® Strain - Transgenic Species laboratory mouse Background Strain NOD Donor Strain FVB Donating Investigator Paul Epstein, University of Louisville H2 Haplotype g7 Strain 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.Strain 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.
Related Disease (OMIM) Terms |
Mammalian Phenotype Terms assigned by genotype |
Gene & Allele Details
| Allele Symbol | Tg(INS-MT2A,Tyr)1Pne | ||
|---|---|---|---|
| Allele Name | transgene insertion 1, Paul N Epstein | ||
| 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] | ||
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001976 NOD/ShiLtJ | ||
| Considerations for Choosing Controls | ||
Colony Maintenance
| Diet Information | LabDiet® 5K52/5K67 |
|---|
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
Research Applications
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
References
Selected Reference(s)
Additional ReferencesChen 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]
Price and Supply Information
| Strain Name: | NOD.FVB-Tg(INS-MT2A,Tyr)1Pne/PneJ |
| Stock Number: | 005115 |
Price Details
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Supply Details
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. |
| Licensing | See General Terms and Conditions below |
| Control Information | View Control Information in Strain Details. |
General Terms and Conditions
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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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