Strain Name:

NOD-Tg(Igh-6/Igh-V281)3Jwt/JwtJ

Stock Number:

005020

Availability:

Repository-Cryopreserved

Description

Strain Information

Type Mutant Strain; Transgenic;
Additional information on Genetically Engineered Mutant Mice.
Specieslaboratory mouse
Background Strain NOD
Donor Strain NOD/MrkTacfBR
H2 Haplotypeg7
 
Donating Investigator James Thomas,   Vanderbilt University

Appearance
albino, pink-eyed
Related Genotype: A/A Tyrc/Tyrc

Description
The double transgenic produced by crossing this stock with Stock No. 005018 serves as a control to the double transgenic which results from crossing Stock No. 005018 with Stock No. 005019.

Development
Thomas and Hulbert received the BALB/c IgG1 mouse anti-human insulin monoclonal antibody, mAb125 from the American Type Culture Collection (ATCC). This mab cross-reacts to mouse insulin. It was found that the variable region of the heavy chain of mAb125 has some sequence differences from the germ line sequence that generated this antibody sequence, referred to as VH-IX-281. When residues 49 and 56 of the variable region of the heavy chain of mAb125 are mutated back to the residues found in the germ line sequence, the resulting antibody no longer binds insulin with high affinity. The construct for Tg(Igh-6/Igh-V281)3Jwt has these germ line reversions (from G to D at residue 49 and from E to V at residue 56). This VDJ sequence, with these two residue changes, was cloned in place of the endogenous variable sequence downstream of the Igh-6 sequence in the construct previously used by Goodenow et al., to generate anti-hen egg lysozyme transgenes. This new construct encodes an IgMa constant region with a variable region nearly identical to that of mAB125 but lacking the high affinity specificity for insulin. This construct was microinjected into NOD/Tac oocytes and the transgenic strain has been mated to NOD/Tac for 7 generations. In 2004, N7 mice were backcrossed to NOD/LtJ at The Jackson Laboratory, and are maintained hemizygote x wild type.

Control Information

  Control
   Noncarrier
   001976 NOD/ShiLtJ
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying other alleles of Igh-6     (12 strains)

View Strains carrying other alleles of Igh-V     (3 strains)

Additional Web Information

Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

Tg(Igh-6/Igh-V281)3Jwt/0

        NOD.B6-Tg(Igh-6/Igh-V281)3Jwt
  • endocrine/exocrine gland phenotype
  • insulitis (MGI Ref ID J:91865)
    • by 40 weeks, pancreata of transgenic mice show extensive infiltrates
  • immune system phenotype
  • decreased susceptibility to autoimmune diabetes (MGI Ref ID J:91865)
    • transgenic mice are protected from developing diabetes; 16% develop diabetes by 40 weeks
  • insulitis (MGI Ref ID J:91865)
    • by 40 weeks, pancreata of transgenic mice show extensive infiltrates
  • digestive/alimentary phenotype
  • insulitis (MGI Ref ID J:91865)
    • by 40 weeks, pancreata of transgenic mice show extensive infiltrates
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)
Type 1 Diabetes (IDDM) Analysis Strains (NOD Transgenics)

Research Tools
Diabetes and Obesity Research

Igh-6 related

Immunology and Inflammation Research
Immunodeficiency (B cell deficiency)

Research Tools
Cancer Research (B cell deficiency)
Immunology and Inflammation Research (B cell deficiency)

Genes & Alleles

Gene & Allele Information

Allele Symbol Tg(Igh-6/Igh-V281)3Jwt
Allele Name transgene insertion 3, James W Thomas
Allele Type Transgenic (random, expressed)
Common Name(s) 281HC; H125.gl; VH281; VH281Tg;
Mutation Made By James Thomas,   Vanderbilt University
Strain of OriginC57BL/6
Expressed Gene Igh-V, immunoglobulin heavy chain variable region, mouse, laboratory
Expressed Gene Igh-6, immunoglobulin heavy chain 6 (heavy chain of IgM), mouse, laboratory
Promoter Igh-6, immunoglobulin heavy chain 6 (heavy chain of IgM), mouse, laboratory
Molecular Note The construct for Tg(Igh-6/Igh-V281)3Jwt has a germ line reversion encoding D at residue 49 (from G)and another encoding V (from E) at residue 56. The transgene encodes an IgMa constant region with a variable region nearly identical to that ofthe BALB/c IgG1 mouse anti-human insulin monoclonal antibody, mAb125, (from the American Type Culture Collection) but lacking the high affinity specificity for insulin. [MGI Ref ID J:91865]

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)

Rojas M; Hulbert C; Thomas JW. 2001. Anergy and not clonal ignorance determines the fate of B cells that recognize a physiological autoantigen. J Immunol 166(5):3194-200. [PubMed: 11207272]  [MGI Ref ID J:91866]

Additional References

Tg(Igh-6/Igh-V281)3Jwt related

Hulbert C; Riseili B; Rojas M; Thomas JW. 2001. B cell specificity contributes to the outcome of diabetes in nonobese diabetic mice. J Immunol 167(10):5535-8. [PubMed: 11698422]  [MGI Ref ID J:91865]

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.
  • Genomic DNA is available for this strain from the Mouse DNA Resource.

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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