Strain Name: |
NOD/ShiLt(Cg)-Tg(Ins2-GAD2)2Lt/J |
|---|---|
Stock Number: |
005870 |
Availability: | Repository-Cryopreserved |
General Terms and Conditions |
| Former Name |
NOD/Lt(Cg)-Tg(Ins2-GAD2)2Lt/J (Changed: 23-FEB-07
) |
| Strain Common Names | NOD.GAD65; |
| Genes & Alleles | GAD2; Ins2; Tg(Ins2-GAD2)2Lt; |
Product Information
Strain Details
Type JAX® GEMM® Strain - Coisogenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Mutant Strain Type JAX® GEMM® Strain - Transgenic Species laboratory mouse Donating Investigator Edward Leiter, The Jackson Laboratory H2 Haplotype g7 Generation N2+N3F1pN1 Appearance
pink-eyed, albino
Related Genotype: A/A Tyrc/TyrcStrain Description
This transgene expresses human glutamic acid decarboxylase 2 cDNA under the control of the rat insulin 2 promoter. FISH analysis and pseudo-giemsa metaphase spead analysis establish the insertion site of this transgene on proximal Chr 15 near the centromere. Expression of the transgene in the islets has been confirmed by RT-PCR and Western blot analysis. Southern blot analysis confirm 4-5 copies of the transgene are present. Homozygotes are developmentally lethal. Transgene positive animals are significantly protected from diabetes onset (females- 14%, Males- 15% at 50 weeks) compared to NOD/ShiLt controls (Females- 100%, Males-50% by 50 weeks). Insulitis in 9 week old females is not significantly different between transgenics and controls.This model provides a tool for studying at the role of autoantigens, specifically GAD2, in diabetes.
Strain Development
Glutamic acid decarboxylase 2, GAD2 (commonly referred to as GAD65) is highly expressed in human and rat beta cells, but little to no expression in mouse beta cells. Because GAD2 is a major autoantigen candidate in human T1D, a human GAD2 under control of the rat insulin promoter 7, Ins2, was injected directly into NOD/ShiLt zygotes. In 2006, the T1DR received this transgenic strain at generation F?+33. The transgene Ins2-GAD2 encodes the human glutamic acid decarboxylase2 cDNA under the control of the rat insulin 7 promoter. This transgenic construct was injected into NOD/ShiLt oocytes and the resulting founders were backcrossed to wildtype siblings. NOD transgenic mice were backcrossed 1 generation to NOD.CB17-Prkdcscid prior to intercrossing to make homozygote for the Prkdcscid mutation (Bridgett et al, Diabetes 1998 47:1848-56). In 2005, the Type 1 Diabetes Resource received NOD/LtSz-Prkdcscid Tg(Ins2-GAD2)2Lt/LtJ and in 2006 backcrossed to NOD/ShiLtJ (Stock No. 001976) to re-establish the NOD/Lt transgenic strain without the Prkdcscid mutation.
Mammalian Phenotype Terms assigned by genotype |
Gene & Allele Details
| Allele Symbol | Tg(Ins2-GAD2)2Lt | ||
|---|---|---|---|
| Allele Name | transgene insertion 2, Edward H Leiter | ||
| Common Name(s) | TgN(RIP7hGAD65)Lt4 (A line); TgN(RIP7hGAD65)Lt4 A-line; | ||
| Mutation Made By | Edward Leiter, The Jackson Laboratory | ||
| Strain of Origin | NOD/ShiLt | ||
| Expressed Gene | GAD2, glutamate decarboxylase 2 (pancreatic islets and brain, 65kDa), human | ||
| Promoter | Ins2, insulin 2, rat | ||
| Molecular Note | The transgene comprises the cDNA sequence encoding human glutamic acid decarboxylase 2 under control of a modified rat insulin 2 promoter composed of 9.5 kb of genomic DNA from upstream of the transcription initiation site fused to the first intron of Ins2. Densitrometric Southern blot analysis indicates presence of 4-5 copies of the transgene. FISH analysis and pseudo-Giemsa metaphase spread analysis showed integration to have occurred near the centromere of Chr 15. Expression in the pancreatic islets of transgenic mRNA has been demonstrated by reverse transcription followed by PCR (RT-PCR), and of GAD2 protein by western blot analysis. [MGI Ref ID J:100251] | ||
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| Considerations for Choosing Controls | ||
Genotyping Protocols
Tg(Ins2-GAD2)
Colony Maintenance
| Breeding & Husbandry | Homozygotes are lethal. A footpad injection of Complete Freund s Adjuvant (CFA) administered once at weaning will delay diabetes onset, thus extending the lifespan of breeders. Use of Complete Freund s Adjuvant in NOD mice can be found in Current Protocols in Immunology page 15.9.19, Reproduction. |
|---|
Related Strains
Strains carrying Tg(Ins2-GAD2)2Lt allele
003844 NOD.Cg-Prkdcscid Tg(Ins2-GAD2)2Lt/LtJ View Strains carrying Tg(Ins2-GAD2)2Lt (1 strain)
003843 NOD.Cg-Prkdcscid Tg(Ins2-GAD2)1Lt/LtJ 003074 NOD/ShiLt-Tg(Ins2-GAD2)1Lt/LtJ
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)
References
Selected Reference(s)
Bridgett M; Cetkovic-Cvrlje M; O'Rourke R; Shi Y; Narayanswami S; Lambert J; Ramiya V; Baekkeskov S; Leiter EH. 1998. Differential protection in two transgenic lines of NOD/Lt mice hyperexpressing the autoantigen GAD65 in pancreatic beta-cells. Diabetes 47(12):1848-56. [PubMed: 9836515] [MGI Ref ID J:100251]
Price and Supply Information
| Strain Name: | NOD/ShiLt(Cg)-Tg(Ins2-GAD2)2Lt/J |
| Stock Number: | 005870 |
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 |
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. |
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