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Strain Name:

C57BL/6-Tg(Ins2-TFRC/OVA)296Wehi/WehiJ

Stock Number:

005431

Availability:

Repository- Live


General Terms and Conditions

Former Name      C57BL/6-Tg(Ins2-TFRC/OV)296Wehi/WehiJ    (Changed: 01-FEB-07 )
Genes & Alleles   Ins2;   OVA;   TFRC;   Tg(Ins2-TFRC/OVA)296Wehi;


Product Information

Strain Details

Type JAX® GEMM® Strain - Mutant Strain
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Transgenic
Mating System+/+ sibling x Hemizygote         (Female x Male)
Specieslaboratory mouse
Donating Investigator William Heath,   The Walter and Eliza Hall Institute
H2 Haplotypeb
GenerationN20+N1F4 (05-JAN-08)

Appearance
black
Related Genotype: a/a

Strain Description
Ins2-TFRC/OVA (commonly referred to as RIP-mOVA) line 296-1B hemizygote transgenic mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Immunohistochemical analysis detects strong expression in pancreatic beta cells and kidney proximal tubular cells and weak expression in testes.

When C57BL/6-Tg(Ins2-TFRC/OVA)296Wehi/WehiJ is mated to C57BL/6-Tg(TcraTcrb)1100Mjb/J (commonly referred to as OT-1 and recognizes OVA specific T-cells, Stock No. 003831) thymic deletion of OT-1 cells is observed in double transgenic mice, suggesting very low levels of thymic expression. OVA specific CD-8+ T-cells activated by cross presentation infiltrate the pancreas causing beta cell destruction resulting in diabetes. However, these cells do not infiltrate the kidney.

Proliferating OT-1 T-cells appeared specifically in the lymph nodes draining the pancreas (PLN's) and kidney (RLN's) on day 3 after adoptive transfer of naive OT-1 cells into adult C57BL/6-Tg(Ins2-TFRC/OVA)296Wehi/WehiJ hosts. In contrast, no proliferating cells were detected in the PLN's after introduction into 10-d-old recipients, although they were observed in significant numbers in the RLNs of these animals.

This transgenic model has been used to study ectopic expression in the thymus and for assessing the requirements for peripheral deletion.

Strain Development
The fusion transgene TFRC/OVA is under the control of the rat insulin promoter (Ins2) and encodes the first 118 residues of the human transferrin receptor (TFRC), which includes the cytoplasmic tail and signal/anchor domain, fused to mature chicken ovalbumin (OVA), residues 139-38, resulting in a membrane bound form of ovalbumin. This transgenic construct was injected into C57BL/6J oocytes and founder, 296-1B, was backcrossed to C57BL/6J for 20 generations (C Kurts, H Kosaka et al, 1996). In 2005, transgenic line 296-1B arrived at The Jackson Laboratory, was backcrossed to C57BL/6J one generation and is maintained Tg/? x Tg/?.

Mammalian Phenotype Terms assigned by genotype

Tg(Ins2-TFRC/OVA)296Wehi/0

        involves: C57BL/6
  • life span-post-weaning/aging
  • abnormal induced morbidity/mortality (MGI Ref ID J:122114)
    • 75% of mice injected with Tg(TcraTcrb)1100Mjb CD8+ T cells from a Rag1 null mouse and anti-ovalbumin IgG die by day 47
  • immune system phenotype
  • abnormal CD8-positive T cell morphology (MGI Ref ID J:98589)
    • 3 days following injection of OT-1 cells into transgenic animal, OVA-specific CD*+ T cells show activation and 50% of the cells have proliferated in a BrdU assay; injected non-transgenic animals show considerably less activation or proliferation
  • abnormal leukocyte migration/homing (MGI Ref ID J:98589)
    • injection of OVA-specific CD8+ T cell from OT-1 mice into transgenic female mice results in a 2- to 6-fold higher proportion of OT-1 CD8+ T cells/total CD8+ T cells in the kidney and pancreatic lymph nodes compared with mesenteric, inguinal or cervical lymph nodes or the spleen, while no accumulation of OT-1 CD8+ T cells is seen in non transgenic animals
  • decreased interferon-gamma secretion (MGI Ref ID J:122114)
    • mice treated with Tg(TcraTcrb)1100Mjb CD8+ T cells from a Rag1 null mouse without anti-ovalbumin IgG exhibit an IFN-gamma production that is decreased 3-fold compared to in similarly treated Tg(Ins2-TFRC/OVA)296Wehi C3tm1Crr/C3tm1Crrmice
  • increased susceptibility to autoimmune diabetes (MGI Ref ID J:122114)
    • mice injected with Tg(TcraTcrb)1100Mjb CD8+ T cells from a Rag1 null mouse and anti-ovalbumin IgG exhibit increased incidence of diabetes compared to mice receiving Tg(TcraTcrb)1100Mjb CD8+ T cells alone
  • hematopoietic system phenotype
  • abnormal CD8-positive T cell morphology (MGI Ref ID J:98589)
    • 3 days following injection of OT-1 cells into transgenic animal, OVA-specific CD*+ T cells show activation and 50% of the cells have proliferated in a BrdU assay; injected non-transgenic animals show considerably less activation or proliferation

Gene & Allele Details

Allele Symbol Tg(Ins2-TFRC/OVA)296Wehi
Allele Name transgene insertion 296, Walter and Eliza Hall Institute of Medical Research
Common Name(s) RIP-mOVA;
Mutation Made By William Heath,   The Walter and Eliza Hall Institute
Strain of OriginC57BL/6
Expressed Gene TFRC, transferrin receptor (p90, CD71), human
Expressed Gene OVA, ovalbumin, chicken
Promoter Ins2, insulin 2, rat
General Note Ovalbumin (OV) is present at high levels in pancreatic beta cells and in kidney proximal tubule cells and at very low levels in testes of transgenic mice. No OV has been detected immunohistologically in any of multiple other tissues examined. Mice expressing both this transgene and Tg(Tcra,Tcrb)1100Mjb (OT-1), which encodes an OV-specific T cell receptor expressed on CD8+ T lymphocytes, exhibit thymic deletion of OT-1 T cells, indicating presence of OV at very low levels in the thymus. Western blot analysis reproducibly measured the pancreatic islet OV content as 2.2 ng/ug of protein.
Molecular Note The transgene encodes a fusion protein comprising the carboxy-terminal 118 amino acids of the human transferrin receptor, which include the cytoplasmic tail, membrane-targeting signal and anchor domain of the protein, joined to amino acids 139-385 of mature ovalbumin. Its expression is directed by the rat insulin 2 promoter. [MGI Ref ID J:98589]

Control Information

  Control
   Noncarrier
 
  Considerations for Choosing Controls

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

Related Strains

Strains carrying other alleles of Ins2
005534   B10.Cg-H2d Tg(Ins2-HA)165Bri/ShrmJ
005500   B6.C-Tg(Ins2-GP)34-20Olds/MvhJ
005715   B6.Cg H2g7-Tg(Ins2-CD80)3B7Flv/LwnJ
004826   B6.Cg-Tg(Ins2-NP)25-3Olds/MhvJ
003573   B6.Cg-Tg(Ins2-cre)25Mgn/J
005713   C.Cg-Tg(Ins2-CD80)3B7Flv/LwnJ
005533   C.Cg-Tg(Ins2-HA)165Bri/ShrmJ
004827   C.Cg-Tg(Ins2-NP)25-3Olds/MvhJ
005432   C57BL/6-Tg(Ins2-OVA)307Wehi/WehiJ
005433   C57BL/6-Tg(Ins2-OVA)59Wehi/WehiJ
005564   FVB(Cg)-Tg(Ins2-CALM1)26Ove Tg(Cryaa-TAg)1Ove/PneJ
008232   FVB/N-Tg(Ins2-IAPP)RHFSoel/J
005522   NOD-Tg(Ins2*Y16A)1Ell/GseJ
005523   NOD-Tg(Ins2*Y16A)3Ell/GseJ
003499   NOD-Tg(Ins2-Fasl)24Ach
007840   NOD.Cg-Prkdcscid Tg(Ins2-CD86)12B70Flv/FswJ
004346   NOD.Cg-Prkdcscid Tg(Ins2-CD80)3B7Flv/DvsJ
004230   NOD.Cg-Prkdcscid Tg(Ins2-E3)1Dvs/DvsJ
003843   NOD.Cg-Prkdcscid Tg(Ins2-GAD2)1Lt/LtJ
003844   NOD.Cg-Prkdcscid Tg(Ins2-GAD2)2Lt/LtJ
005524   NOD.Cg-Tg(Ins2*Y16A)1Ell Ins1tm1Jja Ins2tm1Jja/GseJ
005525   NOD.Cg-Tg(Ins2*Y16A)3Ell Ins1tm1Jja Ins2tm1Jja/GseJ
006254   NOD.Cg-Tg(Ins2-Ccl21b)2Cys/JbsJ
006154   NOD.Cg-Tg(Ins2-Cxcl13)1Cys/JbsJ
003869   NOD.Cg-Tg(Ins2-E3)1Dvs/DvsJ
005685   NOD.Cg-Tg(Ins2-HA)165Bri/ShrmJ
002380   NOD.Cg-Tg(Ins2-TAg)1Lt Prkdcscid/DvsJ
004602   NOD.Cg-Tg(Ins2-rtTA)2Doi/DoiJ
004937   NOD.Cg-Tg(Ins2-tTA)1Doi/DoiJ
005734   NOD/Lt-Tg(Ins2-rtTA)1Ach/AchJ
005870   NOD/ShiLt(Cg)-Tg(Ins2-GAD2)2Lt/J
006777   NOD/ShiLt-Tg(Ins2-Cd274)2Mdos/MdosJ
005733   NOD/ShiLt-Tg(Ins2-Fas*I246N)1Ach/AchJ
003074   NOD/ShiLt-Tg(Ins2-GAD2)1Lt/LtJ
004986   NOD/ShiLt-Tg(Ins2-cre)3Lt/Lt
003855   NOD/ShiLt-Tg(Ins2-cre)5Lt/LtJ
004987   NOD/ShiLt-Tg(Ins2-cre)6Lt/Lt
002033   NOD/ShiLt-Tg(RipTAg)1Lt/J
004990   NOD/ShiLtDvs-Tg(Ins2-E3*734)4Dvs/DvsJ
005714   NOR.Cg-Tg(Ins2-CD80)3B7Flv/LwnJ
008122   STOCK Tg(Ins2-cre/Esr1)1Dam/J
008250   STOCK Tg(Ins2-rtTA)2Efr/J
View Strains carrying other alleles of Ins2     (42 strains)

Strains carrying other alleles of OVA
005145   C57BL/6-Tg(CAG-OVA)916Jen/J
005432   C57BL/6-Tg(Ins2-OVA)307Wehi/WehiJ
005433   C57BL/6-Tg(Ins2-OVA)59Wehi/WehiJ
View Strains carrying other alleles of OVA     (3 strains)

Animal Health Reports

Room Number           FGB29

Research Applications

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

Immunology and Inflammation Research
Autoimmunity (Type 1 Diabetes)
CD Antigens, Antigen Receptors, and Histocompatibility Markers

Research Tools
Diabetes and Obesity Research
Immunology and Inflammation Research (T Cell Receptor Transgenics)

References

Selected Reference(s)

Kurts C; Heath WR; Carbone FR; Allison J; Miller JF; Kosaka H. 1996. Constitutive class I-restricted exogenous presentation of self antigens in vivo. J Exp Med 184(3):923-30. [PubMed: 9064352]  [MGI Ref ID J:98589]

Additional References

Price and Supply Information

Strain Name: C57BL/6-Tg(Ins2-TFRC/OVA)296Wehi/WehiJ
Stock Number: 005431

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Supply Details

Standard SupplyRepository-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.
Supply Notes Usually shipped between four and eight weeks of age.
This strain is included in the Type 1 Diabetes Repository collection.
LicensingSee General Terms and Conditions below  
Control InformationView Control Information in Strain Details.

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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