Strain Name:

NOD.129S2(B6)-Ins2tm1Jja/GseJ

Stock Number:

005036

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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/ShiLtJ
Donor Strain 129S2
H2 Haplotypeg7
GenerationN12+N4F4+N1p
Generation Definitions
 
Donating Investigator George Eisenbarth,   U of Colorado

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

Important Note
NOD-Ins2 KO Diabetes incidence study performed at The Jackson Laboratory show that 90 percent of both male and female homozygous animals become diabetic by 13 weeks of age, however diabetes in untreated homozygous males and females has been identified as early as 4-5 weeks of age.

Description
Ins2tm1Jja heterozygous mice are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities.

RT-PCR detects no expression of Ins2 in the thymus or pancreas of Ins2tm1Jja homozygous mice and Insulin Autoantibody Assays (IAA) indicate that by four weeks of age insulin auto-antibodies were significantly higher than NOD controls. Diabetes incidence occurs in 100 percent of the homozygous females by 15 weeks of age compared with 77% wildtype females by 27 weeks of age. While 100 percent of the homozygote males are diabetic by 22 weeks old compared to 28 percent of the wildtype males by 27 weeks of age. Histological evaluation found extensive islet infiltration in 8 week old homozygous mice compared to wildtype mice in which a minority of islets were infiltrated.

NOD.129S2(B6)-Ins2tm1Jja/GseJ is useful for studying insulin autoantigens and their role in the autoimmune process leading to Type 1 Diabetes.

Development
A construct containing a lacZ-neomycin fusion gene replacing most of the Ins2 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). These mice were then backcrossed to transfer the mutation to NOD (Thebault-Baumont et al, 2003). NOD alleles have been selected for the 16 Idd suseptibility markers, including I-Ag7MHC allele. In 2004, N12 mice were received from Dr. Eisenbath's laboratory and backcrossed to NOD/LtJ twice prior to intercrossing.

Control Information

  Control
   001976 NOD/ShiLtJ
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying   Ins2tm1Jja     (2 strains)

View Strains carrying other alleles of Ins2     (15 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).
Diabetes Mellitus, Insulin-Dependent; IDDM
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Diabetes Mellitus, Insulin-Dependent, 2   (INS)
Diabetes Mellitus, Permanent Neonatal; PNDM   (INS)
Insulin; INS   (INS)
Maturity-Onset Diabetes of the Young, Type 10; MODY10   (INS)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Ins2tm1Jja/Ins2tm1Jja

        NOD.129S2-Ins2tm1Jja
  • homeostasis/metabolism phenotype
  • abnormal glucose homeostasis
    • development of diabetes is accelerated compared to wild-type controls; all but one female develop diabetes between 7 and 15 weeks of age   (MGI Ref ID J:85309)
  • immune system phenotype
  • increased anti-insulin autoantibody level
    • both males and females have higher peak levels of insulin autoantibodies than wild-type   (MGI Ref ID J:85309)
  • insulitis
    • severe insulitis with primarily intraislet infiltrates   (MGI Ref ID J:85309)
  • endocrine/exocrine gland phenotype
  • insulitis
    • severe insulitis with primarily intraislet infiltrates   (MGI Ref ID J:85309)
View Research Applications

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

Ins2tm1Jja 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 Ins2tm1Jja
Allele Name targeted mutation 1, Jacques Jami
Allele Type Targeted (Reporter)
Common Name(s) Ins2-; proins-2-; proinsulin 2-;
Mutation Made By Jacques Jami,   INSERM
Strain of Origin129S2/SvPas
ES Cell Line NameD3
ES Cell Line Strain129S2/SvPas
Gene Symbol and Name Ins2, insulin II
Chromosome 7
Gene Common Name(s) AA986540; IDDM2; ILPR; IRDN; Ins-2; InsII; MODY10; Mody; Mody4; expressed sequence AA986540; maturity onset diabetes of the young; maturity onset diabetes of the young 4;
Molecular Note The majority of the coding region was replaced by the insertion of a lacZ-neo fusion gene. The expression of lacZ was found to be under the control of the endogenous promoter via cytochemical assays. [MGI Ref ID J:40377]

Genotyping

Genotyping Information

Genotyping Protocols

Ins2tm1Jja,

Separated MCA
Ins2tm1Jja, Melt Curve Analysis
Ins2tm1Jja, Standard PCR
Ins2tm1Jjaalternate1, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Thebault-Baumont K; Dubois-Laforgue D; Krief P; Briand JP; Halbout P; Vallon-Geoffroy K; Morin J; Laloux V; Lehuen A; Carel JC; Jami J; Muller S; Boitard C. 2003. Acceleration of type 1 diabetes mellitus in proinsulin 2-deficient NOD mice. J Clin Invest 111(6):851-7. [PubMed: 12639991]  [MGI Ref ID J:82522]

Additional References

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]

Ins2tm1Jja related

Alejandro EU; Lim GE; Mehran AE; Hu X; Taghizadeh F; Pelipeychenko D; Baccarini M; Johnson JD. 2011. Pancreatic beta-cell Raf-1 is required for glucose tolerance, insulin secretion, and insulin 2 transcription. FASEB J 25(11):3884-95. [PubMed: 21817126]  [MGI Ref ID J:180723]

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]

Dubois-Lafforgue D; Mogenet L; Thebault K; Jami J; Krief P; Boitard C. 2002. Proinsulin 2 knockout NOD mice: a model for genetic variation of insulin gene expression in type 1 diabetes. Diabetes 51 Suppl 3:S489-93. [PubMed: 12475795]  [MGI Ref ID J:107164]

Duvillie B; Bucchini D; Tang T; Jami J; Paldi A. 1998. Imprinting at the mouse Ins2 locus: evidence for cis- and trans-allelic interactions. Genomics 47(1):52-7. [PubMed: 9465295]  [MGI Ref ID J:45695]

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]

Faideau B; Briand JP; Lotton C; Tardivel I; Halbout P; Jami J; Elliott JF; Krief P; Muller S; Boitard C; Carel JC. 2004. Expression of preproinsulin-2 gene shapes the immune response to preproinsulin in normal mice. J Immunol 172(1):25-33. [PubMed: 14688305]  [MGI Ref ID J:87572]

Faideau B; Lotton C; Lucas B; Tardivel I; Elliott JF; Boitard C; Carel JC. 2006. Tolerance to proinsulin-2 is due to radioresistant thymic cells. J Immunol 177(1):53-60. [PubMed: 16785498]  [MGI Ref ID J:134383]

Hodish I; Absood A; Liu L; Liu M; Haataja L; Larkin D; Al-Khafaji A; Zaki A; Arvan P. 2011. In vivo misfolding of proinsulin below the threshold of frank diabetes. Diabetes 60(8):2092-101. [PubMed: 21677281]  [MGI Ref ID J:186814]

Jarchum I; DiLorenzo TP. 2010. Ins2 deficiency augments spontaneous HLA-A*0201-restricted T cell responses to insulin. J Immunol 184(2):658-65. [PubMed: 19966211]  [MGI Ref ID J:159429]

Jasinski JM; Yu L; Nakayama M; Li MM; Lipes MA; Eisenbarth GS; Liu E. 2006. Transgenic insulin (B:9-23) T-cell receptor mice develop autoimmune diabetes dependent upon RAG genotype, H-2g7 homozygosity, and insulin 2 gene knockout. Diabetes 55(7):1978-84. [PubMed: 16804066]  [MGI Ref ID J:111874]

Lamotte L; Jackerott M; Bucchini D; Jami J; Joshi RL; Deltour L. 2004. Knock-in of diphteria toxin A chain gene at Ins2 locus: effects on islet development and localization of Ins2 expression in the brain. Transgenic Res 13(5):463-73. [PubMed: 15587270]  [MGI Ref ID J:94589]

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; 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

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.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & Husbandry NOD-Ins2 KO diabetes incidence study performed at The Jackson Laboratory show that 90 percent of both male and female homozygous animals become diabetic by 13 weeks of age, however diabetes in untreated homozygous males and females has been identified as early as 4-5 weeks of age. Recommended breeding scheme is heterozygous x heterozygous or heterozygous female x homozygous male.

A footpad injection of Complete Freund s Adjuvant (CFA) administered once at weaning will delay diabetes onset, thus extending the lifespan of breeders, both heterozygous and homozygous. Use of Complete Freund s Adjuvant in NOD mice can be found in Current Protocols in Immunology page 15.9.19, Reproduction.

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* $2250.00
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.

Embryos

Price (US dollars $)
Frozen Embryo $1600.00

Standard Supply

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

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. 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, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • 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 11 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* $2925.00
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.

Embryos

Price (US dollars $)
Frozen Embryo $2080.00

Standard Supply

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

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. 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, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • 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 11 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.

Control Information

  Control
   001976 NOD/ShiLtJ
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

Important Note

NOD-Ins2 KO Diabetes incidence study performed at The Jackson Laboratory show that 90 percent of both male and female homozygous animals become diabetic by 13 weeks of age, however diabetes in untreated homozygous males and females has been identified as early as 4-5 weeks of age.

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