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Former Names NOR.Cg-Tg(Ins2-CD80)3B7Flv/FswJ (Changed: 07-MAR-06 ) Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain NOR/Lt Donor Strain (C57BL/6 X CBA)F2 H2 Haplotype g7 Generation N11p+F2N1 Donating Investigator Li Wen, Yale School of Medicine Appearance
albino, pink eyed
Related Genotype: A/A Tyrc/TyrcDescription
Transgenic mice are characterized by pancreatic beta cells that express a rat insulin promoter (Ins2) regulated transgene encoding the human CD80 T cell co-stimulatory molecule. These mice are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. Approximately 50% of the NOR (backcross 5) transgenic mice become diabetic by 30 weeks of age compared the control NOR which is diabetes resistant. Spleens of diabetic NOR transgenic mice used in adoptive transfer experiments transfer diabetes to NOD.scid/RIP-B7.1 and irradiated non-diabetic NOR.Cg-Tg(Ins2-CD80)3B7Flv/FswJ mice, yet failed to transfer disease to NOD.scid, B6.scid, or CB17.scid.NOR.-Tg(Ins2-CD80)3B7Flv/FswJ provides a tool for studying mechanisms for loss of tolerance in potentially diabetogenic CD8 T-cells.
Development
A transgenic construct containing the human CD80 gene driven by the rat insulin promoter 1 (RIP) was injected fertilized eggs of a mating between C57BL/6 and CBA/Ca strains in the laboratory of Dr. Richard Flavell (Yale University). Founder animals were obtained and bred to C57BL/6 mice and subsequently mated to NOR/Lt or BALB/c for 10 generations and B6.Cg-H2g7 for 1 generation. In 2005, The Jackson Laboratory received this NOR.Cg-Tg(Ins2-CD80)3B7Flv/FswJ at N10.
| Control | ||
|---|---|---|
| 002050 NOR/LtJ | (approximate) | |
| Considerations for Choosing Controls | ||
Strains carrying Tg(Ins2-CD80)3B7Flv allele
005715 B6.Cg H2g7-Tg(Ins2-CD80)3B7Flv/LwnJ 005713 C.Cg-Tg(Ins2-CD80)3B7Flv/LwnJ 004346 NOD.Cg-Prkdcscid Tg(Ins2-CD80)3B7Flv/DvsJ View Strains carrying Tg(Ins2-CD80)3B7Flv (3 strains)
Strains carrying other alleles of Ins2
View Strains carrying other alleles of Ins2 (42 strains)
Congenic Nomenclature
View Related Disease (OMIM) Terms
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(Ins2-CD80)3B7Flv/?
involves: C57BL/6 * CBA/Ca * NOD/Caj
- endocrine/exocrine gland phenotype
- insulitis (MGI Ref ID J:26618)
- H2g7 homozygous transgenic mice show islet disruption with lymphocytic (T and B cell) infiltration, similar to diabetic NOD controls
- N2 mice after a subsequent backcross to NOD show islet disruption with lymphocytic infiltration as early as 4 weeks while non-transgenic H2g7 homozygous or heterozygous littermates show varying degrees of insulitis by ~6 weeks
- immune system phenotype
- increased susceptibility to autoimmune diabetes (MGI Ref ID J:26618)
- 2/17 transgenic mice from the first cross to NOD develop diabetes between 10 and 14 weeks, compared to no diabetes in (NOD x C57BL/6)F1 non-transgenic controls
- after a further backcross to NOD, diabetes onset is accelerated relative to transgenic mice from the initial cross to NOD with some developing diabetes at 4 weeks; by 12 weeks, 46.2% of transgenic mice homozygous for H2g7 develop diabetes compared to no non-transgenic H2g7 homozygous littermates, or NOD controls which only start to exhibit diabetes at 12 weeks
- insulitis (MGI Ref ID J:26618)
- H2g7 homozygous transgenic mice show islet disruption with lymphocytic (T and B cell) infiltration, similar to diabetic NOD controls
- N2 mice after a subsequent backcross to NOD show islet disruption with lymphocytic infiltration as early as 4 weeks while non-transgenic H2g7 homozygous or heterozygous littermates show varying degrees of insulitis by ~6 weeks
- renal/urinary system phenotype
- increased urine glucose level (MGI Ref ID J:26618)
- homeostasis/metabolism phenotype
- increased circulating glucose level (MGI Ref ID J:26618)
- transgenic mice exhibit blood glucose in excess of 13.9 mmol (250 mg/dl)
- increased urine glucose level (MGI Ref ID J:26618)
- digestive/alimentary phenotype
- insulitis (MGI Ref ID J:26618)
- H2g7 homozygous transgenic mice show islet disruption with lymphocytic (T and B cell) infiltration, similar to diabetic NOD controls
- N2 mice after a subsequent backcross to NOD show islet disruption with lymphocytic infiltration as early as 4 weeks while non-transgenic H2g7 homozygous or heterozygous littermates show varying degrees of insulitis by ~6 weeks
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:
Diabetes and Obesity Research
Type 1 Diabetes (IDDM) Analysis Strains (NOD Transgenics)
Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
Research Tools
Diabetes and Obesity Research
| Allele Symbol | Tg(Ins2-CD80)3B7Flv | ||
|---|---|---|---|
| Allele Name | transgene insertion 3B7, Richard Flavell | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | RIP-B7; RIP-B7-1; RIP-B7.1; RIP-CD80; | ||
| Mutation Made By | Richard Flavell, Yale University School of Medicine | ||
| Strain of Origin | (C57BL/6 x CBA/Ca)F2 | ||
| Expressed Gene | CD80, CD80 molecule, human | ||
| Promoter | Ins2, insulin 2, rat | ||
| General Note | Mice carrying this transgene that also are homozygous for Prkdcscid are characterized by pancreatic beta cells that express a rat insulin II promoter regulated transgene encoding the human CD80 T cell co-stimulatory molecule. | ||
| Molecular Note | The transgene contains a human CD80 antigen gene driven by the rat insulin II promoter (Ins2). [MGI Ref ID J:88250] | ||
Genotyping Protocols
Tg(Ins2-CD80)3B7Flv, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
Tg(Ins2-CD80)3B7Flv relatedDevendra D; Jasinski J; Melanitou E; Nakayama M; Li M; Hensley B; Paronen J; Moriyama H; Miao D; Eisenbarth GS; Liu E. 2005. Interferon-alpha as a mediator of polyinosinic:polycytidylic acid-induced type 1 diabetes. Diabetes 54(9):2549-56. [PubMed: 16123342] [MGI Ref ID J:129147]
Devendra D; Paronen J; Moriyama H; Miao D; Eisenbarth GS; Liu E. 2004. Differential immune response to B:9-23 insulin 1 and insulin 2 peptides in animal models of type 1 diabetes. J Autoimmun 23(1):17-26. [PubMed: 15236749] [MGI Ref ID J:91669]
Guerder S; Eynon EE; Flavell RA. 1998. Autoimmunity without diabetes in transgenic mice expressing beta cell-specific CD86, but not CD80: parameters that trigger progression to diabetes. J Immunol 161(5):2128-40. [PubMed: 9725204] [MGI Ref ID J:93555]
Guerder S; Picarella DE; Linsley PS; Flavell RA. 1994. Costimulator B7-1 confers antigen-presenting-cell function to parenchymal tissue and in conjunction with tumor necrosis factor alpha leads to autoimmunity in transgenic mice. Proc Natl Acad Sci U S A 91(11):5138-42. [PubMed: 7515187] [MGI Ref ID J:88250]
Havari E; Lennon-Dumenil AM; Klein L; Neely D; Taylor JA; McInerney MF; Wucherpfennig KW; Lipes MA. 2004. Expression of the B7.1 costimulatory molecule on pancreatic beta cells abrogates the requirement for CD4 T cells in the development of type 1 diabetes. J Immunol 173(2):787-96. [PubMed: 15240665] [MGI Ref ID J:91915]
Marron MP; Graser RT; Chapman HD; Serreze DV. 2002. Functional evidence for the mediation of diabetogenic T cell responses by HLA-A2.1 MHC class I molecules through transgenic expression in NOD mice. Proc Natl Acad Sci U S A 99(21):13753-8. [PubMed: 12361980] [MGI Ref ID J:109851]
Rajagopalan G; Kudva YC; Chen L; Wen L; David CS. 2003. Autoimmune diabetes in HLA-DR3/DQ8 transgenic mice expressing the co-stimulatory molecule B7-1 in the beta cells of islets of Langerhans. Int Immunol 15(9):1035-44. [PubMed: 12917255] [MGI Ref ID J:85223]
Serra P; Amrani A; Yamanouchi J; Han B; Thiessen S; Utsugi T; Verdaguer J; Santamaria P. 2003. CD40 ligation releases immature dendritic cells from the control of regulatory CD4+CD25+ T cells. Immunity 19(6):877-89. [PubMed: 14670304] [MGI Ref ID J:86995]
Skak K; Haase C; Michelsen BK. 2005. Preservation of beta-cell function during immune-mediated, B7-1-dependent alpha-cell destruction. Eur J Immunol 35(9):2583-90. [PubMed: 16078275] [MGI Ref ID J:113486]
Stephens LA; Kay TW. 1995. Pancreatic expression of B7 co-stimulatory molecules in the non-obese diabetic mouse. Int Immunol 7(12):1885-95. [PubMed: 8746558] [MGI Ref ID J:30235]
Thomas IJ; Petrich de Marquesini LG; Ravanan R; Smith RM; Guerder S; Flavell RA; Wraith DC; Wen L; Wong FS. 2007. CD86 has sustained costimulatory effects on CD8 T cells. J Immunol 179(9):5936-46. [PubMed: 17947667] [MGI Ref ID J:138692]
Ueno A; Cho S; Cheng L; Wang Z; Wang B; Yang Y. 2005. Diabetes resistance/susceptibility in T cells of nonobese diabetic mice conferred by MHC and MHC-linked genes. J Immunol 175(8):5240-7. [PubMed: 16210629] [MGI Ref ID J:119112]
Wen L; Chen NY; Tang J; Sherwin R; Wong FS. 2001. The regulatory role of DR4 in a spontaneous diabetes DQ8 transgenic model. J Clin Invest 107(7):871-80. [PubMed: 11285306] [MGI Ref ID J:68641]
Wen L; Peng J; Li Z; Wong FS. 2004. The effect of innate immunity on autoimmune diabetes and the expression of Toll-like receptors on pancreatic islets. J Immunol 172(5):3173-80. [PubMed: 14978124] [MGI Ref ID J:88224]
Wen L; Wong FS; Tang J; Chen NY; Altieri M; David C; Flavell R; Sherwin R. 2000. In vivo evidence for the contribution of human histocompatibility leukocyte antigen (HLA)-DQ molecules to the development of diabetes. J Exp Med 191(1):97-104. [PubMed: 10620608] [MGI Ref ID J:59245]
Wong FS; Du W; Thomas IJ; Wen L. 2005. The influence of the major histocompatibility complex on development of autoimmune diabetes in RIP-B7.1 mice. Diabetes 54(7):2032-40. [PubMed: 15983204] [MGI Ref ID J:109830]
Wong S; Guerder S; Visintin I; Reich EP; Swenson KE; Flavell RA; Janeway CA Jr. 1995. Expression of the co-stimulator molecule B7-1 in pancreatic beta-cells accelerates diabetes in the NOD mouse. Diabetes 44(3):326-9. [PubMed: 7533734] [MGI Ref ID J:26618]
Currently there no information available for this strain. This may be due to the supply level of this strain.
| Pricing for USA, Canada and Mexico shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
| Pricing for International shipping destinations |
|
*Price(s) in US dollars ($)
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 |
|
| Control | ||
|---|---|---|
| 002050 NOR/LtJ | (approximate) | |
| 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. | ||
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