NOD.FVB-Tg(INS-SOD2)3Pne/PneJ

Stock number: 005113
Product name: NOD.MnSOD
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These NOD.MnSOD mice express a transgene containing a full-length human mitochondrial superoxide dismutase cDNA and show an increase in SOD2 activity in transgenic islets.

Detailed description

Transgenic mice are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. Immunohistochemical staining with mitochondrial superoxide dismutase specific antibody confirms INS-SOD2 transgene expression localized to the mitochondria of pancreatic islet cell. There is a significant increase in SOD2 activity in transgenic islets when compared to wild-type controls. There is no statistical difference in insulin and DNA content, insulin staining and islet morphology or diabetes development following cyclophosphamide treatment between mutant and wild type NOD mice. Transgenic mice are resistant to diabetes when treated with streptozotocin. Islet beta cells from transgenics generate less ROS when treated with peroxynitrite or superoxide. Untreated mutants do not display accelerated spontaneous diabetes.

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

Development

NOD.FVB-Tg(INS-SOD2)3Pne/PneJ expresses the full-length human mitochondrial superoxide dismutase cDNA controlled by the human insulin promoter. The transgene was first inserted into FVB oocytes. Founder line 3, maintained by Epstein et al., has been backcrossed to NOD for at least 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(INS- SOD2)3Pne/PneJ at generation N8F7.

Allele

Symbol: Tg(INS-SOD2)3Pne
Name: transgene insertion 3, Paul N Epstein
MGI accession ID: MGI:3525180
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: IsNOD; MnSOD3
Marker symbol: Tg(INS-SOD2)3Pne
Marker name: transgene insertion 3, Paul N Epstein
Marker synonyms: IsNOD; MnSOD3
Chromosome: UN
Strain of origin: FVB
Expressed genes: SOD2,superoxide dismutase 2,human
Molecular note: The transgene expresses the full-length human mitochondrial superoxide dismutase cDNA controlled by the human insulin promoter. Immunohistochemical staining with mitochondrial superoxide dismutase specific antibody confirms transgene expression localized to the mitochondria of pancreatic islet cell.
General note: Five transgenic lines were generated on an FVB background. This line expressed the highest SOD2 activity.

Transgenic mice are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. There is an approximately 10 fold increase in SOD2 activity in transgenic islets when compared to wild-type controls. There is no statistical difference in insulin and DNA content, insulin staining and islet morphology or diabetes development following cyclophosphamide treatment between mutant and wild-type NOD mice. Transgenic mice are resistant to diabetes when treated with streptozotocin. Islet beta cells from transgenics generate less ROS when treated with peroxynitrite or superoxide. Untreated mutants do not display accelerated spontaneous diabetes.