Strain Name:

NOD-Tg(H2-Ea-Ins2)1Wehi/WehiJ

Stock Number:

005739

Availability:

Repository-Cryopreserved

Common Names: MHCII-Ins2;     Mins II;     NOD-PI;     NOD.MHCII-Ins2;    

Description

Strain Information

Type Coisogenic; Mutant Strain; Transgenic;
Additional information on Genetically Engineered Mutant Mice.
Specieslaboratory mouse
H2 Haplotypeg7
 
Donating Investigator Leonard Harrison,   Walter and Eliza Hall Institute of Medic

Appearance
pink-eyed, albino

Related Genotype: A/A Tyrc/Tyrc

Description
Transgenic mice are viable, fertile, normal in size, normoglycemic and do not display any gross physical or behavioral abnormalities. RT/PCR indicates transgene expression in the spleen and thymus. Blood glucose levels of transgenic and non-transgenic littermates are identical. 90-98 % of the transgenic islets of females and males are insulitis free. Transgenic mice do not develop spontaneous diabetes and are resistant to cyclophosphamide-induced diabetes. Sialitis is not statistically different between transgenic and littermate controls (French MB, Diabetes 1997 46:34-9). Transgenic bone marrow transplanted into 4-week-old irradiated NOD female’s almost entirely prevented diabetes compared to control NOD to irradiated NOD transplants, which have an overall diabetes incidence similar to untreated controls. Thymoma incidence was similar in both irradiated groups.(Steptoe RJ, J Clin Invest 2003 111:1357-63)
This model may be helpful for looking at antigen specific immunotherapeutic strategies for preventing T1D and other autoimmune diseases.

Development
The H2-Ea-Ins2 transgene encodes the protein coding region of mouse preproinsulin II (Ins2) amplified from genomic NOD DNA, controlled by an MHC class II, I-E alphak, promoter. The transgenic fragment was directly injected into NOD/LtWehi oocytes and has been maintained on an NOD/LtWehi background. In 2005, the T1DR received NOD-Tg(H2-Ea-Ins2)1Wehi/WehiJ transgenic mice and mated to NOD/LtJ prior to mating Tg x Tg.

Control Information

  Control
   001976 NOD/ShiLtJ (approximate)
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of H2-Ea
002035   NOD/ShiLt-Tg(H2-Ead)12Lt/J
002034   NOD/ShiLt-Tg(H2-Ead)5Lt/J
001658   STOCK Tg(H2-Ea)16Dim/J
001901   STOCK Tg(H2-Ea*deltaX)16Dim/J
001812   STOCK Tg(H2-Ea*deltaY)54Dim/J
View Strains carrying other alleles of H2-Ea     (5 strains)

View Strains carrying other alleles of Ins2     (9 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

Tg(H2-Ea-Ins2)1Wehi/0

        NOD/LtJWehi-Tg(H2-Ea-Ins2)1Wehi
  • endocrine/exocrine gland phenotype
  • *normal* endocrine/exocrine gland phenotype (MGI Ref ID J:100232)
    • unlike wild-type NOD mice, transgenic NOD/LtWehi mice do not develop spontaneous diabetes
    • whereas wildtype NOD mice are susceptible to diabetes induction by cyclophosphamide, no transgenic NOD/LtWehi mice became diabetic (defined as blood glucose > 11 mmol/l) after a single cyclophosphamide injection; following a second injection only one of ten developed diabetes, and it was more slowly progressive than in wild-type controls
    • pancreata of transgenic NOD/LtWehi mice are almost entirely free of insulitis: 90% of 244 islets from 100-day-old female mice and 98% of 259 islets from 147-day-old males had no cellular infiltration, and the rest exhibited only a minimal degree of insulitis
    • salivary gland inflammation (MGI Ref ID J:100232)
      • the transgene does not affect the characteristic susceptibility of NOD mice to sialitis, the degree of which does not differ significantly between transgenic NOD/LtWis mice and control littermates
  • immune system phenotype
  • *normal* immune system phenotype (MGI Ref ID J:100232)
    • pancreata of transgenic NOD/LtWehi mice are almost entirely free of insulitis: 90% of islets from 100-day-old female mice and 98% of those from 147-day-old males have no cellular infiltration, and the rest exhibit only a minimal degree of insulitis
    • abnormal T cell proliferation (MGI Ref ID J:100232)
      • spleen- and draining lymph node-derived T cells from wild-type and transgenic NOD/LtWehi mice exhibit statistically similar in vitro proliferative responses to peptides derived from proinsulin and GAD2 (GAD65) following immunization with these self antigens
    • salivary gland inflammation (MGI Ref ID J:100232)
      • the transgene does not affect the characteristic susceptibility of NOD mice to sialitis, the degree of which does not differ significantly between transgenic NOD/LtWis mice and control littermates
  • digestive/alimentary phenotype
  • salivary gland inflammation (MGI Ref ID J:100232)
    • the transgene does not affect the characteristic susceptibility of NOD mice to sialitis, the degree of which does not differ significantly between transgenic NOD/LtWis mice and control littermates
  • hematopoietic system phenotype
  • abnormal T cell proliferation (MGI Ref ID J:100232)
    • spleen- and draining lymph node-derived T cells from wild-type and transgenic NOD/LtWehi mice exhibit statistically similar in vitro proliferative responses to peptides derived from proinsulin and GAD2 (GAD65) following immunization with these self antigens

Tg(H2-Ea-Ins2)1Wehi/Tg(H2-Ea-Ins2)1Wehi

        NOD/LtJWehi-Tg(H2-Ea-Ins2)1Wehi
  • immune system phenotype
  • *normal* immune system phenotype (MGI Ref ID J:117352)
    • G6pc2206-214-specific T cells have cytotoxic potential in vitro but are 'ignorant' of their antigen
    • dendritic cell antigen presentation to dendritic cells from wild-type NOD mice; antigen presenting cell function is not affected
    • abnormal CD8-positive T cell morphology (MGI Ref ID J:117352)
      • T cells specific for IGRP206-214 (G6pc2206-214) are almost undetectable in absence of priming in peripheral blood or lymphoid tissues in NOD mice expressing the transgene, at any age assayed, while such cells are readily detected and peak at 15 weeks of age in wild-type NOD controls
    • decreased T cell proliferation (MGI Ref ID J:117352)
      • G6pc2206-214-specific CD8+ T cells transferred from Tg(TcraTcrbNY8.3)1Pesa NOD mice proliferate with much lower efficiency compared to cells transferred to wild-type NOD hosts
      • no regulatory T cell generation is indicated by thymic expression of autoantigens
    • decreased anti-insulin autoantibody level (MGI Ref ID J:117352)
      • mice do not show an insulin autoantibody response, compared to wild-type NOD controls
  • hematopoietic system phenotype
  • *normal* hematopoietic system phenotype (MGI Ref ID J:117352)
    • abnormal CD8-positive T cell morphology (MGI Ref ID J:117352)
      • T cells specific for IGRP206-214 (G6pc2206-214) are almost undetectable in absence of priming in peripheral blood or lymphoid tissues in NOD mice expressing the transgene, at any age assayed, while such cells are readily detected and peak at 15 weeks of age in wild-type NOD controls
    • decreased T cell proliferation (MGI Ref ID J:117352)
      • G6pc2206-214-specific CD8+ T cells transferred from Tg(TcraTcrbNY8.3)1Pesa NOD mice proliferate with much lower efficiency compared to cells transferred to wild-type NOD hosts
      • no regulatory T cell generation is indicated by thymic expression of autoantigens
View Research Applications

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

Diabetes and Obesity Research
Type 1 Diabetes (IDDM) (resistant)
Type 1 Diabetes (IDDM) Analysis Strains (NOD Transgenics)

Immunology and Inflammation Research
Autoimmunity (Type 1 Diabetes)
CD Antigens, Antigen Receptors, and Histocompatibility Markers

Research Tools
Diabetes and Obesity Research

Ins2 related

Diabetes and Obesity Research
Type 1 Diabetes (IDDM) Analysis Strains (NOD/ShiLtJ Non-MHC Congenics)

Immunology and Inflammation Research
Autoimmunity (Type 1 Diabetes)

Genes & Alleles

Gene & Allele Information

Allele Symbol Tg(H2-Ea-Ins2)1Wehi
Allele Name transgene insertion 1, William and Eliza Hall Institute
Allele Type Transgenic (random, expressed)
Mutation Made By Leonard Harrison,   Walter and Eliza Hall Institute of Medic
Strain of OriginNOD/ShiLt
Expressed Gene Ins2, insulin II, mouse, laboratory
Promoter H2-Ea, histocompatibility 2, class II antigen E alpha, mouse, laboratory
General Note Two lines of mice were created with this trasgenic construct on the NOD background. No distinction was made between them.
Molecular Note The transgene comprises nucleotides -1,903 through -39 of the 5' flanking sequence of the MHC Class II gene H2-Ea (k allele), containing the promoter, followed by a 909 base pair mouse (NOD strain) genomic DNA fragment containing the sequence encoding prepronsulin II and the SV40 small t intron and polyadenylation signal.

Transgene-derived mRNA is detectable in spleen and thymus of transgenic NOD/LtWehi mice, but not of control littermates, by reverse transcription followed by PCR (RT/PCR) using either primers for H2-Eak and proinsulin or two proinsulin primers. Immunoreactive proinsulin is detectable in medium from cultured transgenic splenocytes only after 8 days' culture and at levels 10-2 - 10-3 times those of cultured islets or islet cells; levels are increased by culture with interferon gamma and tumor necrosis factor alpha. [MGI Ref ID J:100232]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(H2-Ea-Ins2)1Wehi, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

French MB; Allison J; Cram DS; Thomas HE; Dempsey-Collier M; Silva A; Georgiou HM; Kay TW; Harrison LC; Lew AM. 1997. Transgenic expression of mouse proinsulin II prevents diabetes in nonobese diabetic mice. Diabetes 46(1):34-9. [PubMed: 8971078]  [MGI Ref ID J:100232]

Additional References

Tg(H2-Ea-Ins2)1Wehi related

Krishnamurthy B; Dudek NL; McKenzie MD; Purcell AW; Brooks AG; Gellert S; Colman PG; Harrison LC; Lew AM; Thomas HE; Kay TW. 2006. Responses against islet antigens in NOD mice are prevented by tolerance to proinsulin but not IGRP. J Clin Invest 116(12):3258-65. [PubMed: 17143333]  [MGI Ref ID J:117352]

Krishnamurthy B; Mariana L; Gellert SA; Colman PG; Harrison LC; Lew AM; Santamaria P; Thomas HE; Kay TW. 2008. Autoimmunity to Both Proinsulin and IGRP Is Required for Diabetes in Nonobese Diabetic 8.3 TCR Transgenic Mice. J Immunol 180(7):4458-4464. [PubMed: 18354167]  [MGI Ref ID J:132969]

Health & husbandry

Health & Colony Maintenance Information

Currently there no information available for this strain. This may be due to the supply level of this strain.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Pricing for USA, Canada and Mexico shipping destinations View International pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $1900.00
Cryopreserved Embryos Fee $1600.00
*Price(s) in US dollars ($)

Additional Supply Details

Pricing for International shipping destinations View USA Canada and Mexico pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $2470.00
Cryopreserved Embryos Fee $2080.00
*Price(s) in US dollars ($)

Additional Supply Details

Supply Details

Standard SupplyRepository-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.
    One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845.

  • This strain is included in the Type 1 Diabetes Repository collection.

Control Information

  Control
   001976 NOD/ShiLtJ (approximate)
 
  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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