Overview

Also Known As: BALB.RIP NP

These BALB.RIP NP mice express a transgene containing the nucleoprotein from Armstrong's clone of the lymphocytic choriomeningitis virus (LCMV), and develop IDDM after challenge with LCMV. BALB.RIP NP mice show a slower onset of IDDM than B6.RIP NP (Stock No. 004826) when challenged with LCMV.

Donating Investigator

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

Genetic overview

Genetic Background	Generation

Tg(Ins2-NP)25-3Olds

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) nucleoprotein(NP) or glycoprotein(GP) under the control of the rat insulin promoter. Northern blot analysis identifies a 3kb band expected of the transgene and SV40 processing signals in the pancreas (Oldstone et al., 1991). Ins2-NP expression was determined in the pancreas and thymus by RT-PCR (von Herrath et al 1994). Tg(Ins2-NP)25-3Olds untreated mice rarely develop insulin-dependent diabetes mellitus (IDDM). When challenged with LCMV they develop IDDM. The B6.Cg -Tg(Ins2-NP)25-3Olds mice (H2^b) exhibit a slower (30-120 days) onset of IDDM than the C.Cg-Tg(Ins2-NP)25-3Olds mice (H2^d) (10-21 days) or the B6.Cg-Tg(Ins2-GP) 34-20Olds mice (H2^b) (10-14 days) (Oldstone et al.,1991, Homann et al.,1999). Thymic expression of nucleoprotein has been shown to be responsible for this delayed onset of IDDM. Thymi from newborn B6.Cg-Tg(Ins2-NP)25-3Olds transplanted into hosts homozygous for Prkdc^scid fail to produce a primary CTL response when challenged with LCMV, although thymi transplanted from C.Cg-Tg(Ins2-NP)25-3Olds mice mount a response. CD8 T cells are required for IDDM development in both nucleoprotein and glycoprotein transgenic mice, as is interferon gamma. In interferon gamma deficient transgenicsstimulated 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)

Diabetes can be prevented in the C.Cg-Tg(Ins2-NP)25-3Olds (H2^dmice after its induction by LCMV infection through oral insulin treatment and this model has proven that bystander suppression of autoaggressive CD8 T cells can occur in the pancreatic draining lymph node (Homann et al., 1999).

A single dose injection of anti CD80, anti CD86 or anti CD80/anti CD86 antibodies does not prevent LCMV induced diabetes in either the NP or GP 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 thatconfer 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

C.Cg-Tg(Ins2-NP)25-3Olds/MvhJ expresses the lymphocytic choriomeningitis virus (LCMV) nucleoprotein (NP) 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 25-3, maintained by Herrath et al., (1994, 2000) has been backcrossed to BALB/c (H2^d) for at least 10 generations. This strain arrived at The Jackson Laboratory in 2003 and is maintained as hemizygous.

Expression Data

Expressed Gene	NP, lymphocytic choriomeningitis virus nucleoprotein, viral
Site of Expression

Control Suggestions

Noncarrier

Approximate Controls

000651 BALB/cJ

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-NP)25-3Olds

Allele Symbol: Tg(Ins2-NP)25-3Olds

Allele Name	transgene insertion 25-3, Michael BA Oldstone, MD
Allele Type	Transgenic (Inserted expressed sequence)
Allele Synonym(s)	Tg(Ins2-NP)25-3Olds; transgene insertion 25-3, Michael BA Oldstone, MD
Gene Symbol and Name	Tg(Ins2-NP)25-3Olds, transgene insertion 25-3, Michael BA Oldstone, MD
Gene Synonym(s)	RIP-LCMV; RIP NP 25-3; RIP-LCMV NP
Promoter	Ins2, insulin 2, rat
Expressed Gene	NP, lymphocytic choriomeningitis virus nucleoprotein, viral
Strain of Origin	C57BL/6 x BALB/c
Chromosome	UN
Molecular Note	This transgene encodes the nucleoprotein (NP) from Armstrong's clone of the lymphocytic choriomeningitis virus (LCMV) regulated by the rat insulin promoter. Upstream of the NP cDNA are 660 base pairs of regulatory elements in addition to the rat insulin promoter. Downstream of the NP c-DNA is the SV40 small T-antigen intron and late polyadenylation signal. A stable transcript of the expected size was present in the pancreas, as determined by Northern blot analysis. RT-PCR analysis demonstrated that the transcript was expressed in pancreas and thymus, but not the spleen, brain, liver, kidney, heart, muscle or lung. In a T cell recognition assay, LCMV-specific cytotoxic T lymphocytes were shown to migrate specifically to the islets of Langerhans of transgenic mice, but not in control mice.
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
  - T Cell Receptor Transgenics
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-NP)25-3Olds/0
involves: BALB/c * C57BL/6

endocrine/exocrine gland phenotype

abnormal pancreatic islet morphology
- Background Sensitivity - after viral challenge, mononuclear cells infiltrate the islets of transgenic mice bred onto a BALB/c background at 14-21days, while mice bred onto a C57BL/6 background show infiltrates at 21-60 days
- mononuclear cells begin infiltrating the islets 10 days after viral challenge and are apparent in most transgenic mice after 30 days
- pancreata of diabetic transgenic mice show swollen islets with a ground glass appearance

homeostasis/metabolism phenotype

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

increased circulating glucose level
- 3% of transgenic mice develop diabetes when followed for 10-12 months
- 93% of transgenic mice develop diabetes (hyperglycemia of >250 mg/dl glucose and islets infiltrated with mononuclear cells) after being infected with LCMV
- mice are considered diabetic after a blood glucose measure of >300 mg/dl

immune system phenotype

decreased susceptibility to autoimmune diabetes
- depletion of CD8+ lymphocytes with a monoclonal antibody inhibited development of diabetes

increased susceptibility to autoimmune diabetes
- 3% of transgenic mice develop diabetes when followed for 10-12 months
- 93% of transgenic mice develop diabetes (evidenced by hyperglycemia with glucose levels of >300 mg/dl and islets infiltrated with mononuclear cells) after being infected with LCMV
- Background Sensitivity - after viral (LCMV) challenge, transgenic mice bred onto a C57BL/6 background develop diabetes in 3-5 months, whereas transgenic mice bred onto a BALB/c background develop diabetes sooner, at 1-2 months

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 References

von Herrath MG; Dockter J; Oldstone MB. 1994. How virus induces a rapid or slow onset insulin-dependent diabetes mellitus in a transgenic model. Immunity 1(3):231-42PubMed: 7889411 MGI: J:81287

Additional - Tg(Ins2-NP)25-3Olds related

Technical Support

Contact Technical Support

Genotyping Protocols
- Separated PCR: Tg(Ins2-NP)25-3Olds
- Genotyping resources and troubleshooting
Mating System
- +/+ sibling x Hemizygote
Appearance
- albino
  Related Genotype: A/A Tyr^c/ Tyr^c
Citation
When using the BALB.RIP NP mouse strain in a publication, please cite the originating article(s) and include JAX stock #004827 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-NP)25-3Olds

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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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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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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Licensing Information

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Also Known As: BALB.RIP NP

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Tg(Ins2-NP)25-3Olds

Allele Symbol: Tg(Ins2-NP)25-3Olds

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-NP)25-3Olds/0involves: BALB/c * C57BL/6

endocrine/exocrine gland phenotype

homeostasis/metabolism phenotype

immune system phenotype

References

Additional References

Additional - Tg(Ins2-NP)25-3Olds 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

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-NP)25-3Olds/0
involves: BALB/c * C57BL/6