NOD.FVB-Tg(Ins1-Cat,Tyr)25Pne/PneJ

Stock number: 005114
Product name: NOD.RIP-Cat
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These NOD.RIP-Cat mice express a transgene containing a rat catalase cDNA and show an increase in catalase activity.

Detailed description

Transgenic mice are viable, fertile, and normal in size, display accelerated spontaneous diabetes onset in males, and have coat color pigmentation. Northern blot analysis and immunohistochemistry confirm pancreatic islet specific expression of the Ins1-Cat transgene. There is a 50-fold increase in catalase activity in transgenic islets when compared to wild-type controls, which approximates catalase activity normally found in the liver. Insulin and DNA content, insulin staining and islet morphology in transgenic animals is essentially the same as in wild-type controls.

Transgenic islets have a similar reactive oxygen species (ROS) level as wild-type controls in normal media. However, after exposure to cytokines there is a significant increase of ROS fluorescence in control islets, but much smaller increase in transgenic islets. Transgenic mice are resistant to diabetes when treated with streptozotocin or alloxan. Transgenic beta cells generate less ROS fluorescence when treated with hydrogen peroxide, superoxide or peroxynitrite, but surprisingly cyclophosphamide accelerates diabetes onset in transgenic mice.

This model provides a tool for looking at the role of oxidative stress in diabetes.

Development

NOD.FVB-Tg(Ins1-Cat, Tyr)25Pne/PneJ expresses the full-length rat catalase cDNA under the control of the rat insulin 1 promoter. In addition, these mice express tyrosinase under the control of the tyrosinase promoter, commonly referred to as TyBs or tyrosinase minigene (Xu et al, 1999, Overbeek et al., 1991). These transgenes were first co-inserted by Xu et al., (1999) into FVB oocytes. Transgenic founders carrying both genes were mated to FVB and found to co-segregate. This strain was maintained by Epstein et al., and backcrossed to NOD for 8 generations. A genome wide scan confirmed that all known Idd markers were homozygous for the NOD allele. In 2004, The Jackson Laboratory received NOD.FVB-Tg(Ins1-Cat,Tyr)25Pne/PneJ at generation N8F7.

Allele

Symbol: Tg(Ins1-Cat,Tyr)25Pne
Name: transgene insertion 25, Paul N Epstein
MGI accession ID: MGI:3043843
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(Ins1-Cat,Tyr)25Pne
Marker name: transgene insertion 25, Paul N Epstein
Chromosome: UN
Strain of origin: FVB
Expressed genes: Cat,catalase,rat
Molecular note: The symbol represents a double transgene. In one transgene, a rat insulin I promoter drives the expression of a rat catalase cDNA. Northern blot analysis and immunohistochemistry detected expression of this transgene in pancreatic beta cells. A second transgene that expresses tyrosinase under control of the tyrosinase promoter was coinjected with the first transgene, and apparently cosegregated.