NOD.FVB-Tg(Igh-6-Cd80)1Gjf/JbsJ

Stock number: 007769
Strain synonyms: NOD-B7-1B Tg
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

This congenic NOD strain contains a transgene encoding murine Cd80 controlled by IgM enhancer and promoter elements and is commonly referred to as NOD.B7-1B Tg. The donating investigator reports that this diabetes resistant strain expresses high levels of the transgene on B cells, but not on T-cells. Circulating, speenic, and bone marrow B cells are significantly reduced. This strain may be used to study autoreactive T cell activation, B cell deletion and the role of B7 co stimulatory molecules in autoimmunity, specifically Type 1 Diabetes.

Detailed description

Transgenic mice are viable, fertile, normal in size, normoglycemic and do not display any gross physical or behavioral abnormalities. High levels of the transgene are expressed on B cells, but not on T cells. At 30 weeks of age transgenic mice are diabetes resistant and insulitis was significantly reduced when compared with wildtype NOD controls. When compared to wildtype NOD controls, the circulating B cells in congenic NOD transgenic mice is 2-3 fold lower in 2 week old mice and 10 fold lower in 5-6 week old mice and persists throughout life. Significantly reduced percentage of B cells were found in the spleen and bone marrow. Analysis of bone marrow shows the more mature B cell subsets (B220+, IgM+) are affected. Elisa tests indicate reduced circulating levels of all Ig types, Ighm (formerly Igh-6), Igh-3 (IgG2b), and Ighg1 (IgG1) in the serum of transgenic mice. MHC class II expression of splenic B cells was significantly increased by more than 2 fold, indicating features of an activated B cell phenotype, in NOD-H2^g7 transgenic mice when compared to NOD wildtype and NOD.-H2^b transgenic mice.

In 2008, a spontaneous mutation to dystonia (Dst) was observed in this colony and may be segregating in cryopreserved stock.

This strain may be used to study autoreactive T cell activation and B cell deletion and the role of B7 costimulatory molecules in autoimmunity, specifically Type 1 Diabetes.

Development

The Igh-6-CD80 transgenic construct, commonly called B7-1B Tg, encodes a murine Cd80 cDNA, containing the complete coding region that lacks the 2' and 5' UTR's, controlled by IgM enhancer and promoter elements. To enhance expression of the transgene, the construct additionally contains a mutated non-expressible segment of the human growth hormone gene. The transgenic construct was microinjected into FVB/N embryos. FVB/N transgenic mice from line B-B7-1 were backcrossed to NOD/MrkTac mice for more than 15 generations. In 2007, the T1DR received transgenic mice at generation N15⁺ and backcrossed to NOD/ShiLtJ (Stock No. 001976) once prior to sibling mating.

Allele

Symbol: Tg(Igh-6-Cd80)1Gjf
Name: transgene insertion 1, Gordon J Freeman
MGI accession ID: MGI:3656398
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(Igh-6-Cd80)1Gjf
Marker name: transgene insertion 1, Gordon J Freeman
Chromosome: UN
Strain of origin: FVB
Expressed genes: Cd80,CD80 antigen,mouse, laboratory
Molecular note: The transgene was constructed with the Cd80 cDNA containing the complete coding region (but lacking the 2' and 5' UTRs) under control of the Igh-6 enhancer and promoter elements. The construct also contained a mutated nonexpressible segment of the human growth hormone gene included to enhance transgene expression.