NOD-Tg(H2-Ea-Ins2)1Wehi/WehiJ

Stock number: 005739
Product name: NOD.MHCII-Ins2
Strain synonyms: Mins II, NOD-PI
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These mice express a transgene containing the protein coding region of mouse preproinsulin II (Ins2). They do not develop spontaneous diabetes and are resistant to cyclophosphamide-induced diabetes.

Detailed description

Transgenic mice are viable, fertile, normal in size, normoglycemic and do not display any gross physical or behavioral abnormalities. RT/PCR indicates transgene expression in the spleen and thymus. Blood glucose levels of transgenic and non-transgenic littermates are identical. 90-98 % of the transgenic islets of females and males are insulitis free. Transgenic mice do not develop spontaneous diabetes and are resistant to cyclophosphamide-induced diabetes. Sialitis is not statistically different between transgenic and littermate controls (French MB, Diabetes 1997 46:34-9). Transgenic bone marrow transplanted into 4-week-old irradiated NOD females almost entirely prevented diabetes compared to control NOD to irradiated NOD transplants, which have an overall diabetes incidence similar to untreated controls. Thymoma incidence was similar in both irradiated groups.(Steptoe RJ, J Clin Invest 2003 111:1357-63)
This model may be helpful for looking at antigen specific immunotherapeutic strategies for preventing T1D and other autoimmune diseases.

Development

The H2-Ea-Ins2 transgene encodes the protein coding region of mouse preproinsulin II (Ins2) amplified from genomic NOD DNA, controlled by an MHC class II, I-E alpha^k, promoter. The transgenic fragment was directly injected into NOD/LtWehi oocytes and has been maintained on an NOD/LtWehi background. In 2005, the T1DR received NOD-Tg(H2-Ea-Ins2)1Wehi/WehiJ transgenic mice and mated to NOD/LtJ prior to mating Tg x Tg.

Allele

Symbol: Tg(H2-Ea-Ins2)1Wehi
Name: transgene insertion 1, William and Eliza Hall Institute
MGI accession ID: MGI:3590216
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(H2-Ea-Ins2)1Wehi
Marker name: transgene insertion 1, William and Eliza Hall Institute
Chromosome: UN
Strain of origin: NOD/ShiLt
Expressed genes: Ins2,insulin II,mouse, laboratory
Molecular note: The transgene comprises nucleotides -1,903 through -39 of the 5' flanking sequence of the MHC Class II gene H2-Ea (k allele), containing the promoter, followed by a 909 base pair mouse (NOD strain) genomic DNA fragment containing the sequence encoding prepronsulin II and the SV40 small t intron and polyadenylation signal.

Transgene-derived mRNA is detectable in spleen and thymus of transgenic NOD/LtWehi mice, but not of control littermates, by reverse transcription followed by PCR (RT/PCR) using either primers for H2-Ea^k and proinsulin or two proinsulin primers. Immunoreactive proinsulin is detectable in medium from cultured transgenic splenocytes only after 8 days' culture and at levels 10^-2 - 10^-3 times those of cultured islets or islet cells; levels are increased by culture with interferon gamma and tumor necrosis factor alpha.
General note: Two lines of mice were created with this trasgenic construct on the NOD background. No distinction was made between them.