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Journal of Neuroscience, Vol 14, 5844-5857, Copyright © 1994 by Society for Neuroscience
Metallothionein III is expressed in neurons that sequester zinc in synaptic vesicles
BA Masters, CJ Quaife, JC Erickson, EJ Kelly, GJ Froelick, BP Zambrowicz, RL Brinster and RD Palmiter
Laboratory of Reproductive Physiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104.
MT-III, a brain-specific member of the metallothionein gene family, binds
zinc and may facilitate the storage of zinc in neurons. The distribution of
MT-III mRNA within the adult brain was determined by solution and in situ
hybridization and compared to that of MT-I mRNA. MT-III mRNA is
particularly abundant within the cerebral cortex, hippocampus, amygdala,
and nuclei at base of the cerebellum. Transgenic mice generated using 11.5
kb of the mouse MT-III 5' flanking region fused to the E. coli lacZ gene
express beta-galactosidase in many of the same regions identified by in
situ hybridization. MT-III mRNA was present in readily identifiable neurons
within the olfactory bulb, hippocampus, and cerebellum, and
beta-galactosidase activity was localized to neurons throughout the brain,
but not to glia, as determined by costaining with X-Gal and neural- and
glia-specific antibodies. There is marked correspondence between the
neurons that are rich in MT-III mRNA and those neurons that store zinc in
their terminal vesicles. MT-III is found complexed with zinc in vivo and
its expression in cultured cells leads to the intracellular accumulation of
zinc and enhanced histochemical detection of zinc. These results are
discussed in light of the possibility that MT-III may participate in the
utilization of zinc as a neuromodulator.
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