| |||||||||
Type Coisogenic; Congenic; Mutant Strain; Targeted Mutation; Transgenic; Species laboratory mouse Background Strain NOD/MrkTac Donor Strain D3 (129S2/SvPas) H2 Haplotype g7 Generation N10F9+F3p Donating Investigator George Eisenbarth, U of Colorado Appearance
albino, pink eyed
Related Genotype: A/A Tyrc/TyrcDescription
Expression has been reported in the pancreatic islets and thymus of NOD mice carrying the Tg(Ins2*Y16A)3Ell mutation. Approximately 15% of line F female transgenic mice become diabetic in the presence of native insulin genes by 35 weeks of age. NOD female transgenic mice lacking both Ins1 and Ins2 fail to produce insulin autoantibodies, and there is no diabetes or insulitis at 26 weeks of age, but sialitis is present. In contrast, transgenic mice in the presence of Ins1 and lacking Ins2 develop diabetes in 75% of the animals by 25 weeks of age (Nakayama et al, 2004, 2005).This stock is useful to study insulin-reactive autoimmunity.
Development
NOD-Tg(Ins2*Y16A)3Ell/GseJ expresses the rat insulin 7 promoter fused to a mutated preproinsulin II cDNA, where the tyrosine at position 16 of the b chain was replaced with alanine. This transgene was inserted by Nakayama et al, 2004 directly into NOD/MrkTac oocytes. Offspring from the founder line F was further crossed to NOD.Ins1-/- and NOD.Ins2-/- prior to intercrossing for homozygosity of the Ins1 and Ins2 targeted mutations. In 2006, the T1DR received NOD.Cg-Tg(Ins2*Y16A)3Ell Ins1tm1Jja Ins2tm1Jja/GseJ at generation N10F9.
| Control | ||
|---|---|---|
| 005035 NOD.129S2(B6)-Ins1tm1Jja/GseJ | ||
| 005036 NOD.129S2(B6)-Ins2tm1Jja/GseJ | ||
| 001976 NOD/ShiLtJ | ||
| Considerations for Choosing Controls | ||
Strains carrying Ins1tm1Jja allele
005035 NOD.129S2(B6)-Ins1tm1Jja/GseJ 005524 NOD.Cg-Tg(Ins2*Y16A)1Ell Ins1tm1Jja Ins2tm1Jja/GseJ View Strains carrying Ins1tm1Jja (2 strains)
Strains carrying Ins2tm1Jja allele
005036 NOD.129S2(B6)-Ins2tm1Jja/GseJ 005524 NOD.Cg-Tg(Ins2*Y16A)1Ell Ins1tm1Jja Ins2tm1Jja/GseJ View Strains carrying Ins2tm1Jja (2 strains)
Strains carrying Tg(Ins2*Y16A)3Ell allele
005523 NOD-Tg(Ins2*Y16A)3Ell/GseJ View Strains carrying Tg(Ins2*Y16A)3Ell (1 strain)
Strains carrying other alleles of Ins1
006872 B6.Cg-Tg(Ins1-DsRed*T4)32Hara/J 006864 B6.Cg-Tg(Ins1-EGFP)1Hara/J 008173 NOD.Cg-Tg(Ins1-EGFP)1Hara/QtngJ 006866 STOCK Tg(Ins1-DsRed*T4)32Hara/J 006784 STOCK Tg(Ins1-ECFP)24Hara/J View Strains carrying other alleles of Ins1 (5 strains)
Strains carrying other alleles of Ins2
View Strains carrying other alleles of Ins2 (49 strains)
Congenic Nomenclature
Related Disease (OMIM) Terms
NOT Diabetes Mellitus, Insulin-Dependent; IDDM Mammalian Phenotype Terms assigned by genotype
Ins1tm1Jja/Ins1tm1Jja Ins2tm1Jja/Ins2tm1Jja Tg(Ins2*Y16A)3Ell/0
NOD.Cg-Ins1tm1Jja Ins2tm1Jja Tg(Ins2*Y16A)3Ell
- immune system phenotype
- decreased anti-insulin autoantibody level (MGI Ref ID J:98583)
- females lacking both insulin genes do not produce insulin autoantibodies
- decreased susceptibility to autoimmune diabetes (MGI Ref ID J:98583)
- no female double knockout mice carrying the transgene on a NOD background develop diabetes over 30 weeks of observation
- salivary gland inflammation (MGI Ref ID J:98583)
- at 26 weeks of age, sialitis is observed but not insulitis
- digestive/alimentary phenotype
- salivary gland inflammation (MGI Ref ID J:98583)
- at 26 weeks of age, sialitis is observed but not insulitis
- endocrine/exocrine gland phenotype
- salivary gland inflammation (MGI Ref ID J:98583)
- at 26 weeks of age, sialitis is observed but not insulitis
Research Applications
This mouse can be used to support research in many areas including:
Ins1 relatedDiabetes and Obesity Research
Insulin Receptors and Growth Factors
Type 1 Diabetes (IDDM) Analysis Strains (NOD Transgenics)
Type 1 Diabetes (IDDM) Analysis Strains (NOD/ShiLtJ Non-MHC Congenics)
Immunology and Inflammation Research
Autoimmunity (Type 1 Diabetes)
Autoimmunity (autoimmune pancreatitis and sialoadenitis)
Research Tools
Diabetes and Obesity Research
Ins2 relatedDiabetes and Obesity Research
Type 1 Diabetes (IDDM) Analysis Strains (NOD/ShiLtJ Non-MHC Congenics)
Immunology and Inflammation Research
Autoimmunity (Type 1 Diabetes)
Ins1tm1Jja relatedDiabetes and Obesity Research
Type 1 Diabetes (IDDM) Analysis Strains (NOD/ShiLtJ Non-MHC Congenics)
Immunology and Inflammation Research
Autoimmunity (Type 1 Diabetes)
Ins2tm1Jja relatedDiabetes and Obesity Research
Impaired Insulin Processing
Insulin Receptors and Growth Factors
Type 1 Diabetes (IDDM)
Impaired Insulin Processing
Insulin Receptors and Growth Factors
Type 1 Diabetes (IDDM)
| Allele Symbol | Ins1tm1Jja | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Jacques Jami | ||
| Common Name(s) | Ins1-; | ||
| 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 | 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] | ||
| Allele Symbol | Ins2tm1Jja | ||
| Allele Name | targeted mutation 1, Jacques Jami | ||
| 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] | ||
| Allele Symbol | Tg(Ins2*Y16A)3Ell | ||
| Allele Name | transgene insertion 3, John F Elliot | ||
| Common Name(s) | tg B:16 alanine, line F; | ||
| Mutation Made By | John Elliott, University of Alberta | ||
| Strain of Origin | NOD/MrkTac | ||
| Expressed Gene | Ins2, insulin 2, rat | ||
| Promoter | Ins2, insulin 2, rat | ||
| Molecular Note | This transgenic construct contains the rat insulin7 construct of the rat insulin 2 gene fused to a mutated preproinsulin II cDNA where the tyrosine at position 16 of the B chain was replaced with alanine. The transgene is expressed in pancreatic beta cells. [MGI Ref ID J:97755] | ||
Genotyping Protocols
Ins1tm1Jja, SEP PCR, vers. 1
Ins2tm1Jja, STD PCR, vers. 1
Tg(Ins2*Y16A), STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
Hediger MA; Budarf ML; Emanuel BS; Mohandas TK; Wright EM. 1989. Assignment of the human intestinal Na+/glucose cotransporter gene (SGLT1) to the q11.2----qter region of chromosome 22. Genomics 4(3):297-300. [PubMed: 2714793] [MGI Ref ID J:9755]
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]Ins2tm1Jja relatedDuvillie 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]
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]Tg(Ins2*Y16A)3Ell relatedDubois-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]
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]
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]
Nakayama M; Moriyama H; Abiru N; Babu SR; Sikora K; Li M; Miao D; Hutton JC; Elliott JF; Eisenbarth GS. 2004. Establishment of native insulin-negative NOD mice and the methodology to distinguish specific insulin knockout genotypes and a B:16 alanine preproinsulin transgene. Ann N Y Acad Sci 1037:193-8. [PubMed: 15699516] [MGI Ref ID J:97755]
Colony Maintenance
Breeding & Husbandry Genotypes available: Tg/?, Ins1-/-, Ins2-/-
Breeders available: Tg/?, Ins1-/-, Ins2-/- female x Tg/?, Ins1-/-, Ins2-/- male
Affected mutant: Tg/?, Ins1-/-, Ins2-/-
TJL mating scheme: Tg/?, Ins1-/-, Ins2-/- female x Tg/?, Ins1-/-, Ins2-/- male
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
For additional Licensing and Use Restrictions view the link(s) below:
- Strain(s) not available to companies or for-profit entities.
Purchasing Information
JAX® Mice Orders
Surgical Services
Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form