Overview

Also Known As: NOD.RIP-GpLCMV

These transgenic mice carry The lymphocytic choriomeningitis virus (LCMV) glycoprotein and develop insulin-dependent diabetes mellitus when challenged with LCMV.

Donating Investigator

Dr. Matthais von Herrath, La Jolla Institute for Allergy and Immun

Genetic overview

Genetic Background	Generation
000664 C57BL/6J

Tg(Ins2-GP)34-20Olds

Allele Type
Transgenic (Inserted expressed sequence)

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Research Applications

Diabetes and Obesity Research
Research Tools
Immunology, Inflammation and Autoimmunity Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Transgenic mice were created with the Lymphocytic choriomeningitis virus (LCMV) glycoprotein(GP) or nucleoprotein (NP) under the control of the rat insulin promoter. Ins2-GP expression was determined only in the pancreas by RT-PCR (von Herrath et al 1994). Tg(Ins2-GP)34-20Olds untreated mice rarely develop insulin-dependent diabetes mellitus (IDDM). When challenged with LCMV they develop IDDM. The B6.C -Tg(Ins2-GP)34-20Olds mice (H2^b) exhibit a rapid (10-14 days) onset of IDDM compared to C.B6-Tg(Ins2-NP)25-3Olds mice (H2^d) (10-21 days) or B6.C -Tg(Ins2-NP)25-3Olds mice (H2^b) (30-120 days) (Oldstone et al.,1991; von Herrath et al.,1994). Thymic expression of nucleoprotein has been shown to be responsible for this delayed onset of IDDM. Thymi from newborn B6.C -Tg(Ins2-GP)34-20Olds transplanted into nude hosts produce a primary CTL response when challenged with LCMV. CD8 T cells are required for IDDM development in both glycoprotein and nucleoprotein transgenic mice, as is interferon gamma. In interferon gamma deficient transgenics stimulated with LCMV, CTLs were present in the pancreas and around the islets of Langerhans, but did not infiltrate the islets. Additionally, nucleoprotein transgenic animals require the presence of CD4 T cells. (von Herrath, et al, 1994 and 1997)

A singledose injection of anti CD80, anti CD86 or anti CD80/anti CD86 antibodies does not prevent LCMV induced diabetes in either the GP or NP transgenic mice. LCMV challenged GP transgenic mice are partially protected from diabetes by anti CD80 antibodies and completely protected by anti CD86 or anti CD80/CD86 antibodies injected daily for 14 days. However, LCMV challenged NP transgenic mice have accelerated diabetes onset when treated with anti CD80/CD86 antibodies injected daily for 14 days. LCMV induced diabetes is prevented in NP and GP transgenic mice treated with anti TNFRSF5 when treated within a defined time window. Splenocytes from these protected mice adoptively transferred disease resistance to LCMV- challenged pre diabetic GP transgenic mice. The cells that confer protection express ITGAX5, NK1.1 and DX5. The spleens of anti TNFRSF5 protected mice have an increased population of ITGAX5 expressing cells. When this population of cells is further fractionated into ITGAX5⁺, DX5⁺ cells, the recipient mice acquire protection from diabetes. (Homann et al., 2002)

Development

B6.C-Tg(Ins2-GP)34-20Olds/MvhJ expresses the lymphocytic choriomeningitis virus (LCMV) glycoprotein (GP) under control of the rat insulin promoter, (Ins2, commonly designated RIP). The transgene was first inserted by Oldstone, et al (1991) into C57BL/6 (H2^b) x Balb/WEHI (H2^d) F2 oocytes. Line 34-20, maintained by Herrath et al., (1994, 2000) has been backcrossed to C57BL/6 (H2^b) for at least 10 generations. In 2005 this strain arrived at The Jackson Laboratory and is maintained Tg/? x Tg/?.

Expression Data

Expressed Gene	LCMV-GP, lymphocytic choriomeningitis virus glycoprotein,
Site of Expression

Control Suggestions

Noncarrier
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Oldstone MB; Nerenberg M; Southern P; Price J; Lewicki H. 1991. Virus infection triggers insulin-dependent diabetes mellitus in a transgenic model: role of anti-self (virus) immune response. Cell 65(2):319-31PubMed: 1901765 MGI: J:81284

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Genetics

Tg(Ins2-GP)34-20Olds

Allele Symbol: Tg(Ins2-GP)34-20Olds

Allele Name	transgene insertion 34-20, Michael BA Oldstone, MD
Allele Type	Transgenic (Inserted expressed sequence)
Allele Synonym(s)	Tg(Ins2-GP)34-20Olds; transgene insertion 34-20, Michael BA Oldstone, MD
Gene Symbol and Name	Tg(Ins2-GP)34-20Olds, transgene insertion 34-20, Michael BA Oldstone, MD
Gene Synonym(s)	LCMV GP; RIP GP34-20; RIP-LCMV GP; RIP GP H2^b; RIP-GP34-20
Promoter	Ins2, insulin 2, rat
Expressed Gene	LCMV-GP, lymphocytic choriomeningitis virus glycoprotein,
Strain of Origin	(C57BL/6 x BALB/Wehi)F2
Chromosome	UN
Molecular Note	This transgene encodes the glycoprotein (GP) from Armstrong's clone of the lymphocytic choriomeningitis virus (LCMV) regulated by the rat insulin promoter. Upstream of the GP cDNA are 660 base pairs of regulatory elements in addition to the rat insulin promoter. Downstream of the GP c-DNA is the SV40 small T-antigen intron and late polyadenylation signal. RT-PCR analysis demonstrated that the transcript was expressed in the pancreas but not the thymus, spleen, liver, kidney, heart, muscle or lung.
Mutations Made By	Dr. Michael Oldstone, The Scripps Research Institute

Disease/Phenotype

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

type 1 diabetes mellitus

Research Areas By Genotype

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

Diabetes and Obesity Research
- Type 1 Diabetes (IDDM)
Research Tools
- Diabetes and Obesity Research
Immunology, Inflammation and Autoimmunity Research
- Autoimmunity
  - Type 1 Diabetes

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Tg(Ins2-GP)34-20Olds/0
involves: BALB/c * C57BL/6

endocrine/exocrine gland phenotype

abnormal pancreatic islet morphology
- mononuclear cells infiltrate the islets of transgenic mice 5-10 days after viral innoculation

absent pancreatic beta cells
- no beta cells are detected at 14 days after LCMV infection

hematopoietic system phenotype

abnormal lymphocyte physiology
- on a B6 background, transgenic mice cannot exhibit a primary CTL response

abnormal T cell physiology
- depletion of CD8+ lymphocytes with a monoclonal antibody inhibited development of diabetes

homeostasis/metabolism phenotype

decreased circulating insulin level
- hypoinsulinemia is exhibited by transgenic mice accompanying increased glucose levels and islet infiltration

increased circulating glucose level
- mice are considered diabetic after a blood glucose measure of >300 mg/dl

immune system phenotype

abnormal lymphocyte physiology
- on a B6 background, transgenic mice cannot exhibit a primary CTL response

abnormal T cell physiology
- depletion of CD8+ lymphocytes with a monoclonal antibody inhibited development of diabetes

increased susceptibility to autoimmune diabetes
- mice rapidly develop diabetes (glucose levels >300 mg/dl) 10-14 days after viral (LCMV) challenge

References

Oldstone MB; Nerenberg M; Southern P; Price J; Lewicki H. 1991. Virus infection triggers insulin-dependent diabetes mellitus in a transgenic model: role of anti-self (virus) immune response. Cell 65(2):319-31PubMed: 1901765 MGI: J:81284

Additional - Tg(Ins2-GP)34-20Olds related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR: Tg(Ins2-GP)34-20Olds
- Genotyping resources and troubleshooting
Mating System
- +/+ sibling x Hemizygote
Appearance
- black
  Related Genotype: a/a
Citation
When using the NOD.RIP-GpLCMV mouse strain in a publication, please cite the originating article(s) and include JAX stock #005500 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Hemizygous or Non carrier for Tg(Ins2-GP)34-20Olds

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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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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Also Known As: NOD.RIP-GpLCMV

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Tg(Ins2-GP)34-20Olds

Allele Symbol: Tg(Ins2-GP)34-20Olds

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Tg(Ins2-GP)34-20Olds/0involves: BALB/c * C57BL/6

endocrine/exocrine gland phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

References

Additional - Tg(Ins2-GP)34-20Olds related

Genotyping Protocols

Mating System

Appearance

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Genotype: Tg(Ins2-GP)34-20Olds/0
involves: BALB/c * C57BL/6