Cellular clones and transgenic mice overexpressing copper — zinc superoxide dismutase: Models for the study of free radical metabolism and aging

  • Irène Ceballos-Picot
  • Annie Nicole
  • Pierre-Marie Sinet
Part of the EXS book series (EXS, volume 62)


Down’s Syndrome (DS), the most frequent of congenital birth defects, results from the trisomy of the chromosome numbered 21 in all cells of affected patients. This disease is characterized by developmental anomalies, mental retardation and features of rapid aging, particularly in the brain where the occurrence of Alzheimer’s disease (AD) is observed in all trisomy 21 patients over the age of 35. Elucidation of the biological mechanisms leading to brain aging in DS might provide new insight into the understanding of brain aging and AD in normal people.

Copper-zinc superoxide dismutase (CuZnSOD) is one of the genes encoded by chromosome 21. As a consequence of gene dosage excess, CuZnSOD activity and protein are increased by 50% in all DS tissues. The level of CuZnSOD protein and mRNA is particularly high in hippocampal pyramidal neurons susceptible to degenerative processes in AD and in dopaminergic melanized-neurons vulnerable in Parkinson’s disease. Increased CuZnSOD activity in these age-related neurodegenerative disorders might result in H2O2overproduction and subsequently promote peroxidative damages within cells. Increase of seleno-dependent glutathione peroxidase (Se-GPx) in DS cells supports this concept.

In order to test this hypothesis, cell and animal models of CuZnSOD overexpression have been designed. In cells transfected with the human CuZnSOD gene, and increased Se-GPx activity is observed, a situation which mimics DS. In mice transgenic for the human CuZnSOD, the expression pattern of the transgene in the brain is similar to that in humans, and we can observe an increased peroxidation in this tissue. These data, like others in the literature, support the hypothesis that excess CuZnSOD induces an imbalance in the regulation of oxygen-derived free radical production which might result in peroxidative brain damage and possibly contribute to accelerated aging and age-related neuropathology.


Transgenic Mouse Down Syndrome Glutathione Peroxidase Activity Gene Dosage Effect CuZnSOD Activity 
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Copyright information

© Birkhäuser Verlag Basel/Switzerland 1992

Authors and Affiliations

  • Irène Ceballos-Picot
    • 1
  • Annie Nicole
    • 1
  • Pierre-Marie Sinet
    • 1
  1. 1.Laboratoire de Biochimie Génétique, CNRS URA 1335Hôpital Necker-Enfants MaladesParisFrance

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