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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
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Description
Strain Information
Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Heterozygote x Homozygote (Female x Male) Species laboratory mouse Background Strain NOD/ShiLtJ Donor Strain 129S2 H2 Haplotype g7 Generation N12+N2F8 (05-JAN-08) Donating Investigator George Eisenbarth, U of Colorado Appearance
albino
Related Genotype: A/?, Tyrc/TyrcDescription
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
Strains carrying Ins2tm1Jja allele
005524 NOD.Cg-Tg(Ins2*Y16A)1Ell Ins1tm1Jja Ins2tm1Jja/GseJ 005525 NOD.Cg-Tg(Ins2*Y16A)3Ell Ins1tm1Jja Ins2tm1Jja/GseJ View Strains carrying Ins2tm1Jja (2 strains)
006860 B6.129-Ins2Akita Bdkrb2tm1Jfh/SmiJ 006580 B6.Cg-Ins2Akita Ldlrtm1Her/J 004369 B6.Cg-Rag1tm1Mom Ins2Akita/J 003548 C57BL/6-Ins2Akita/J 007562 D2.B6-Ins2Akita/MatbJ 006867 FVB.B6-Ins2Akita/MlnJ 005739 NOD-Tg(H2-Ea-Ins2)1Wehi/WehiJ
Additional Web Information
Congenic Nomenclature
Phenotype
Phenotype Information
Diabetes Mellitus, Insulin-Dependent; IDDM - Models with phenotypic similarity to human disease where etiologies are distinct.2
2 Human genes are associated with this disease. Orthologs of those genes do not appear in the mouse genotype(s).
assigned by genotype
Ins2tm1Jja/Ins2tm1Jja
NOD.129S2-Ins2tm1Jja
- homeostasis/metabolism phenotype
- abnormal glucose homeostasis (MGI Ref ID J:85309)
- development of diabetes is accelerated compared to wild-type controls; all but one female develop diabetes between 7 and 15 weeks of age
- immune system phenotype
- increased anti-insulin autoantibody level (MGI Ref ID J:85309)
- both males and females have higher peak levels of insulin autoantibodies than wild-type
- insulitis (MGI Ref ID J:85309)
- severe insulitis with primarily intraislet infiltrates
- digestive/alimentary phenotype
- insulitis (MGI Ref ID J:85309)
- severe insulitis with primarily intraislet infiltrates
- endocrine/exocrine gland phenotype
- insulitis (MGI Ref ID J:85309)
- severe insulitis with primarily intraislet infiltrates
This mouse can be used to support research in many areas including:Ins2 related
Ins2tm1Jja relatedDiabetes and Obesity Research
Type 1 Diabetes (IDDM) Analysis Strains (NOD/ShiLtJ Non-MHC Congenics)
Immunology and Inflammation Research
Autoimmunity (Type 1 Diabetes)
Diabetes and Obesity Research
Impaired Insulin Processing
Insulin Receptors and Growth Factors
Type 1 Diabetes (IDDM)
Genes & Alleles
Gene & Allele Information
| 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 Origin | 129S2/SvPas | ||
| ES Cell Line Name | D3 | ||
| ES Cell Line Strain | 129S2/SvPas | ||
| Gene Symbol and Name | Ins2, insulin II | ||
| Chromosome | 7 | ||
| Gene Common Name(s) | AA986540; ILPR; IRDN; Ins-2; InsII; 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, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
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 relatedBabaya 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]
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]
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
Animal Health Reports
Room Number FGB29
Colony Maintenance
Mating System Heterozygote x Homozygote (Female x Male) Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $100.00 Female or Male Heterozygous for Ins2tm1Jja $100.00 Female or Male Homozygous for Ins2tm1Jja *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $200.00 Heterozygous for Ins2tm1Jja x Homozygous for Ins2tm1Jja $200.00 Heterozygous for Ins2tm1Jja x Heterozygous for Ins2tm1Jja
Additional Supply Details
| Supply Notes |
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| Pricing for International shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $130.00 Female or Male Heterozygous for Ins2tm1Jja $130.00 Female or Male Homozygous for Ins2tm1Jja *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $260.00 Heterozygous for Ins2tm1Jja x Homozygous for Ins2tm1Jja $260.00 Heterozygous for Ins2tm1Jja x Heterozygous for Ins2tm1Jja
Additional Supply Details
| Supply Notes |
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Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
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Control Information
| Control | ||
|---|---|---|
| 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. | ||
General Terms and Conditions
See Terms of Use
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