Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA) is detected by quantitative solution hybridization analysis of brain. The total metallothionein protein level in mutant mouse brain tissue is reduced by 70 percent. Mutant mice have decreased total zinc levels in brain (88% of wildtype), which does not significantly alter the amount of histochemically reactive free zinc. The greatest reduction of zinc occurs in the hippocampus. Two year old mutant mice exhibit a greater increase of glial fibrillary acidic protein (GFAP) levels than aged matched wildtype mice. Mutant mice are more sensitive to kainic acid induced seizures, experiencing additional neuronal damage in the CA3 region of the hippocampus. This mutant mouse strain may be useful in studies of zinc regulation in neurophysiology.

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These <i>Mt3</i> knock-out mice exhibit reduced total metallothionein protein level with a reduction of zinc in the hippocampus.



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