B6.C-Tg(Ins2-GP)34-20Olds/MvhJ

Stock number: 005500
Product name: NOD.RIP-GpLCMV
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

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

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/?.

Allele

Symbol: Tg(Ins2-GP)34-20Olds
Name: transgene insertion 34-20, Michael BA Oldstone, MD
MGI accession ID: MGI:3573699
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(Ins2-GP)34-20Olds
Marker name: transgene insertion 34-20, Michael BA Oldstone, MD
Chromosome: UN
Strain of origin: (C57BL/6 x BALB/Wehi)F2
Expressed genes: LCMV-GP,lymphocytic choriomeningitis virus glycoprotein,
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.