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Elimination of zinc from synaptic vesicles in the intact mouse brain by disruption of the ZnT3 gene.

The mammalian protein ZnT3 resides on synaptic vesicle membranes of zinc-containing neurons, suggesting its possible role in vesicular zinc transport. We show here that histochemically reactive zinc, corresponding to the zinc found within synaptic vesicles, was undetectable in the brains of mice with targeted disruption of the ZnT3 gene. Total zinc levels in the hippocampus and cortex of these mice were reduced by about 20%. The ultrastructure of mossy fiber boutons, which normally store the highest levels of vesicular zinc, was unaffected. Mice with one normal ZnT3 allele had reduced levels of ZnT3 protein on synaptic vesicle membranes and had intermediate amounts of vesicular zinc. These results demonstrate that ZnT3 is required for transport of zinc into synaptic vesicles and suggest that vesicular zinc concentration is determined by the abundance of ZnT3.

Pubmed ID: 9990090


  • Cole TB
  • Wenzel HJ
  • Kafer KE
  • Schwartzkroin PA
  • Palmiter RD


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

February 16, 1999

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK53013
  • Agency: NINDS NIH HHS, Id: NS18895
  • Agency: NIGMS NIH HHS, Id: T32 GM07270

Mesh Terms

  • Animals
  • Brain
  • Carrier Proteins
  • Cerebellum
  • Cerebral Cortex
  • Gene Expression Regulation
  • Hippocampus
  • Immunohistochemistry
  • Membrane Proteins
  • Mice
  • Mice, Knockout
  • Promoter Regions, Genetic
  • Synaptic Vesicles
  • Zinc