Strain Name:

NOD.129S2(B6)-Ins1tm1Jja/GseJ

Stock Number:

005035

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Availability:

Cryopreserved - Ready for recovery

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
Background Strain NOD
Donor Strain 129S2
H2 Haplotypeg7
 
Donating Investigator George Eisenbarth,   U of Colorado

Appearance
albino
Related Genotype: A/?, Tyrc/Tyrc

Description
Ins1tm1Jja homozygotes are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. There is no detectable expression of Ins1 in the pancreas by RT-PCR and similar levels of insulin auto-antibodies develop in NOD.129S2(B6)-Ins1tm1Jja homozygotes as are found in NOD controls. However, neither homozygous nor heterozygous males develop diabetes, compared with >20% of wild-type littermates, and less than 5% of the Ins1tm1Jja homozygous females and 40% of the heterozygous females become diabetic compared with >80% of wild-type females when followed for 1 year. Histological evaluation found 48 week old homozygous and heterozygous males to have either minimal periinsulitis or no insulitis. Heterozygous females had more extensive insulitis than heterozygous males and homozygous females had minimal intra-ductal infiltrates and no insulitis, whereas wild type littermates had severe insulitis by 37 weeks of age (Moriyama et al, 2003).

NOD.129S2(B6)-Ins1tm1Jja/GseJ (Stock No. 005035) is useful for studying insulin autoantigens and their role in the autoimmune process leading to Type 1 Diabetes.

Development
A construct containing a neomycin expression cassette replacing most of the Ins1 coding sequences, was transfected into D3 (129S2/SvPas derived) embryonic stem cells (ES cells). These ES cells were injected into C57BL/6 blastocysts. Chimeric founders were initially mated to C57BL/6 and subsequently intercrossed to generate homozygotes (Duvillie et al, 1997). Dr. George Eisenbarth s laboratory received B6.129S2-Ins1tm1Jja from Dr. Jacques Jami and backcrossed this mutation to NOD for 11 generations (Moriyama et al, 2003). In 2004, N11 mice were received at The Jackson Laboratory, backcrossed to NOD/LtJ once, and then maintained homozygote x homozygote.

Control Information

  Control
   See control note: Stock number 5352-NOD.129-(D19Mit10-D19Mit54)/GseJ also serves as a control.
   001976 NOD/ShiLtJ
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying   Ins1tm1Jja     (2 strains)

View Strains carrying other alleles of Ins1     (7 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- No similarity to the expected human disease phenotype was found. One or more human genes are associated with this human disease. The mouse genotype may involve mutations to orthologs of one or more of these genes, but the phenotype did not resemble the disease.
Diabetes Mellitus, Insulin-Dependent; IDDM
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Ins1tm1Jja/Ins1tm1Jja

        NOD.129S2-Ins1tm1Jja
  • immune system phenotype
  • decreased susceptibility to autoimmune diabetes
    • homozygotes are resistant to diabetes and insulitis development on the NOD background; whereas 13 of 15 wild-type NOD mice develop insulitis, only 1 of 19 homozygotes develop diabetes   (MGI Ref ID J:85309)
    • homozygous islets transplanted under the kidney capsule of recent onset NOD wild-type mice reversed the hyperglycemia and maintained euglycemia for a week or longer   (MGI Ref ID J:85309)
View Research Applications

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

Ins1tm1Jja related

Diabetes and Obesity Research
Impaired Insulin Processing
Insulin Receptors and Growth Factors
Type 1 Diabetes (IDDM)

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Ins1tm1Jja
Allele Name targeted mutation 1, Jacques Jami
Allele Type Targeted (Null/Knockout)
Common Name(s) Ins1-;
Mutation Made By Jacques Jami,   INSERM
Strain of Origin129S2/SvPas
ES Cell Line NameD3
ES Cell Line Strain129S2/SvPas
Gene Symbol and Name Ins1, insulin I
Chromosome 19
Gene Common Name(s) Ins-1; Ins2-rs1; insulin 2, related sequence 1; insulin I or insulin pseudogene;
Molecular Note The majority of the coding region was replaced with a neomycin selection cassette. RT-PCR analysis showed an absence of transcript in homozygous mutant mice. [MGI Ref ID J:40377]

Genotyping

Genotyping Information

Genotyping Protocols

Ins1tm1Jja, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Deltour L; Leduque P; Blume N; Madsen O; Dubois P; Jami J; Bucchini D. 1993. Differential expression of the two nonallelic proinsulin genes in the developing mouse embryo. Proc Natl Acad Sci U S A 90(2):527-31. [PubMed: 8421685]  [MGI Ref ID J:3904]

Duvillie B; Cordonnier N; Deltour L; Dandoy-Dron F; Itier JM ; Monthioux E ; Jami J ; Joshi RL ; Bucchini D. 1997. Phenotypic alterations in insulin-deficient mutant mice. Proc Natl Acad Sci U S A 94(10):5137-40. [PubMed: 9144203]  [MGI Ref ID J:40377]

Moriyama H; Abiru N; Paronen J; Sikora K; Liu E; Miao D; Devendra D; Beilke J; Gianani R; Gill RG; Eisenbarth GS. 2003. Evidence for a primary islet autoantigen (preproinsulin 1) for insulitis and diabetes in the nonobese diabetic mouse. Proc Natl Acad Sci U S A 100(18):10376-81. [PubMed: 12925730]  [MGI Ref ID J:85309]

Wentworth BM; Schaefer IM; Villa-Komaroff L; Chirgwin JM. 1986. Characterization of the two nonallelic genes encoding mouse preproinsulin. J Mol Evol 23(4):305-12. [PubMed: 3104603]  [MGI Ref ID J:8636]

Ins1tm1Jja related

Babaya N; Nakayama M; Moriyama H; Gianani R; Still T; Miao D; Yu L; Hutton JC; Eisenbarth GS. 2006. A new model of insulin-deficient diabetes: male NOD mice with a single copy of Ins1 and no Ins2. Diabetologia 49(6):1222-8. [PubMed: 16612590]  [MGI Ref ID J:111475]

Duvillie B; Cordonnier N; Deltour L; Dandoy-Dron F; Itier JM ; Monthioux E ; Jami J ; Joshi RL ; Bucchini D. 1997. Phenotypic alterations in insulin-deficient mutant mice. Proc Natl Acad Sci U S A 94(10):5137-40. [PubMed: 9144203]  [MGI Ref ID J:40377]

Duvillie B; Currie C; Chrones T; Bucchini D; Jami J; Joshi RL; Hill DJ. 2002. Increased islet cell proliferation, decreased apoptosis, and greater vascularization leading to beta-cell hyperplasia in mutant mice lacking insulin. Endocrinology 143(4):1530-7. [PubMed: 11897712]  [MGI Ref ID J:106827]

Fan Y; Rudert WA; Grupillo M; He J; Sisino G; Trucco M. 2009. Thymus-specific deletion of insulin induces autoimmune diabetes. EMBO J 28(18):2812-24. [PubMed: 19680229]  [MGI Ref ID J:152798]

Grupillo M; Gualtierotti G; He J; Sisino G; Bottino R; Rudert WA; Trucco M; Fan Y. 2012. Essential roles of insulin expression in Aire(+) tolerogenic dendritic cells in maintaining peripheral self-tolerance of islet beta-cells. Cell Immunol 273(2):115-23. [PubMed: 22297234]  [MGI Ref ID J:181355]

Leroux L; Desbois P; Lamotte L; Duvillie B; Cordonnier N; Jackerott M; Jami J; Bucchini D; Joshi RL. 2001. Compensatory responses in mice carrying a null mutation for Ins1 or Ins2. Diabetes 50 Suppl 1:S150-3. [PubMed: 11272179]  [MGI Ref ID J:77595]

Mehran AE; Templeman NM; Brigidi GS; Lim GE; Chu KY; Hu X; Botezelli JD; Asadi A; Hoffman BG; Kieffer TJ; Bamji SX; Clee SM; Johnson JD. 2012. Hyperinsulinemia drives diet-induced obesity independently of brain insulin production. Cell Metab 16(6):723-37. [PubMed: 23217255]  [MGI Ref ID J:194167]

Mohan JF; Calderon B; Anderson MS; Unanue ER. 2013. Pathogenic CD4(+) T cells recognizing an unstable peptide of insulin are directly recruited into islets bypassing local lymph nodes. J Exp Med 210(11):2403-14. [PubMed: 24127484]  [MGI Ref ID J:206540]

Mohan JF; Petzold SJ; Unanue ER. 2011. Register shifting of an insulin peptide-MHC complex allows diabetogenic T cells to escape thymic deletion. J Exp Med 208(12):2375-83. [PubMed: 22065673]  [MGI Ref ID J:178627]

Moriyama H; Abiru N; Paronen J; Sikora K; Liu E; Miao D; Devendra D; Beilke J; Gianani R; Gill RG; Eisenbarth GS. 2003. Evidence for a primary islet autoantigen (preproinsulin 1) for insulitis and diabetes in the nonobese diabetic mouse. Proc Natl Acad Sci U S A 100(18):10376-81. [PubMed: 12925730]  [MGI Ref ID J:85309]

Moriyama H; Nagata M; Arai T; Okumachi Y; Yamada K; Kotani R; Yasuda H; Hara K; Yokono K. 2007. Insulin as a T cell antigen in type 1 diabetes supported by the evidence from the insulin knockout NOD mice. Diabetes Res Clin Pract 77 Suppl 1:S155-60. [PubMed: 17459508]  [MGI Ref ID J:136741]

Nakayama M; Abiru N; Moriyama H; Babaya N; Liu E; Miao D; Yu L; Wegmann DR; Hutton JC; Elliott JF; Eisenbarth GS. 2005. Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice. Nature 435(7039):220-3. [PubMed: 15889095]  [MGI Ref ID J:98583]

Nakayama M; Babaya N; Miao D; Sikora K; Elliott JF; Eisenbarth GS. 2005. Thymic expression of mutated B16:A preproinsulin messenger RNA does not reverse acceleration of NOD diabetes associated with insulin 2 (thymic expressed insulin) knockout. J Autoimmun 25(3):193-8. [PubMed: 16289958]  [MGI Ref ID J:106579]

Nakayama M; Beilke JN; Jasinski JM; Kobayashi M; Miao D; Li M; Coulombe MG; Liu E; Elliott JF; Gill RG; Eisenbarth GS. 2007. Priming and effector dependence on insulin B:9-23 peptide in NOD islet autoimmunity. J Clin Invest 117(7):1835-43. [PubMed: 17607359]  [MGI Ref ID J:124210]

Peters J; Beechey C. 2004. Identification and characterisation of imprinted genes in the mouse. Brief Funct Genomic Proteomic 2(4):320-33. [PubMed: 15163367]  [MGI Ref ID J:187438]

Schechter R; Beju D; Miller KE. 2005. The effect of insulin deficiency on tau and neurofilament in the insulin knockout mouse. Biochem Biophys Res Commun 334(4):979-86. [PubMed: 16039605]  [MGI Ref ID J:99957]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2525.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3283.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

General Supply Notes

Control Information

  Control
   See control note: Stock number 5352-NOD.129-(D19Mit10-D19Mit54)/GseJ also serves as a control.
   001976 NOD/ShiLtJ
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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