Strain Name:

NOD.129S2(B6)-Ins1tm1Jja/GseJ

Stock Number:

005035

Availability:

Repository-Cryopreserved

Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered Mutant Mice.
Specieslaboratory mouse
Background Strain NOD
Donor Strain 129S2
H2 Haplotypeg7
GenerationN11+N2F3p (29-JAN-06)
 
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

   
   Stock number 5352-NOD.129-(D19Mit10-D19Mit54)/GseJ also serves as a control.
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying   Ins1tm1Jja     (2 strains)

View Strains carrying other alleles of Ins1     (5 strains)

Additional Web Information

Congenic Nomenclature
Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms
NOTDiabetes Mellitus, Insulin-Dependent; IDDM - No similarity to the expected human disease phenotype was found.4
4 One or more human genes are associated with this human disease. The mouse genotype may involve mutations to orthologs of one or more of those genes, but the phenotype did not resemble the disease.
View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

Ins1tm1Jja/Ins1tm1Jja

        NOD.129S2-Ins1tm1Jja
  • immune system phenotype
  • decreased susceptibility to autoimmune diabetes (MGI Ref ID J:85309)
    • 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
    • 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
View Research Applications

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

Ins1 related

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

Immunology and Inflammation Research
Autoimmunity (Type 1 Diabetes)

Ins1tm1Jja related

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

Genes & Alleles

Gene & Allele Information

Allele Symbol Ins1tm1Jja
Allele Name targeted mutation 1, Jacques Jami
Allele Type Targeted (knock-out)
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, SEP PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

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]

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]

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]

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

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

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 $1900.00
*Price(s) in US dollars ($)

Additional Supply Details

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

Additional Supply Details

Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes
  • 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

   
   Stock number 5352-NOD.129-(D19Mit10-D19Mit54)/GseJ also serves as a control.
 
  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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fax:207-288-6655

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