Related Experiment Videos
Cell damage by excess CuZnSOD and Down's syndrome
Y Groner1, O Elroy-Stein, K B Avraham
1Department of Molecular Genetics and Virology, Weizmann Institute of Science, Rehovot, Israel.
Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|January 1, 1994
Summary
Overexpression of the CuZn-superoxide dismutase (CuZnSOD) gene in Down's Syndrome may cause neurobiological abnormalities. Studies in cell and animal models show elevated CuZnSOD impacts neurotransmitter transport and neuromuscular junctions.
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- Down's Syndrome (DS) is linked to trisomy 21, potentially caused by gene overexpression on chromosome 21.
- Elevated CuZn-superoxide dismutase (CuZnSOD) activity is observed in DS patients.
- CuZnSOD gene mutations are implicated in familial ALS, highlighting its role in neuronal disorders.
Purpose of the Study:
- To investigate the role of CuZnSOD gene dosage in the etiology of Down's Syndrome.
- To explore the physiological consequences of CuZnSOD gene overexpression using cellular and animal models.
Main Methods:
- Developed cellular models (PC12 cells) with elevated human CuZnSOD expression.
- Generated transgenic mice carrying the human CuZnSOD gene.
- Analyzed neurotransmitter uptake in cell models and neuromuscular junctions (NMJ) in mice.
Main Results:
- PC12 cells with increased CuZnSOD showed impaired neurotransmitter uptake, specifically affecting chromaffin granule transport.
- Transgenic mice exhibited 1.6 to 6.0-fold increased CuZnSOD activity in the brain.
- Transgenic mice displayed pathological changes in tongue NMJ, including axon degeneration and altered terminal morphology, mirroring changes seen in DS patients.
Conclusions:
- Elevated CuZnSOD activity interferes with biogenic amine transport, potentially contributing to neurobiological deficits in Down's Syndrome.
- CuZnSOD gene dosage is implicated in the pathological abnormalities of tongue neuromuscular junctions observed in Down's Syndrome.