NOD/ShiLtDvs-Tg(IghH280)48Dvs/J

Stock number: 028930
Product name: NOD-PerH
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

NOD-PerH transgenic mice express Ighm (IgM) and Ighd (IgD) heavy chain genes of islet-derived peripherin-specific B cell hybridoma H280. They have accelerated T1D onset with increased insulitis. These mice may be useful when studying the effect of neuronal autoimmunity on T1D development.

Detailed description

NOD-PerH mice express Ighm (IgM) and Ighd (IgD) heavy chain genes of islet-derived peripherin-specific B cell hybridoma H280. Approximately 50% of pancreatic islet associated B lymphocytes in NOD mice recognize the autoantigen peripherin. Peripherin is expressed widely in neuronal cell bodies and axons of the peripheral and central nervous system. Expression of peripherin also occurs in the peri-insular areas of postnatal NOD mice. The H280 clone was chosen since it was isolated from the islets of a recent T1D onset NOD mouse, exhibited strong peripherin binding, and neither its heavy or light chain demonstrate any evidence of affinity maturation.

Hemizygous NOD-PerH mice exhibit greatly accelerated Type 1 diabetes (T1D) onset, at a frequency of between 90-95% by 20 weeks of age. While control NOD/ShiLtJ mice (Stock No. 001976) develop T1D at a frequency of between 80-90% by 30-40 weeks of age. Insulitis development is also accelerated in this strain compared to controls.

When NOD-PerH mice are crossed with NOD-PerL mice, expressing the peripherin-specific B cell hybridoma H280 Igk light chain (Stock No. 028931), resulting NOD-PerIg mice have further accelerated T1D development and insulitis compared to the separate transgenic lines.

Development

The PerH transgenic construct, containing Ighm (IgM) and Ighd (IgD) heavy chain genes of islet-derived peripherin-specific B cell hybridoma H280, was injected into fertilized NOD/LtDvs oocytes by Dr. Dave Serreze (The Jackson Laboratory). This PerH transgene also contains a constant region compnent allowing expression of PerH as an IgM/D isotype of the IgH^a allotype rather than an IgH^b allotype naturally characterizing NOD mice. Progeny of the NOD-PerH transgenic founder 48 were backcrossed to NOD/ShiLtDvs for three generations. Male and female carriers were sent to The Jackson Laboratory Repository to establish a colony.