These Mt3 knock-out mice exhibit reduced total metallothionein protein level with a reduction of zinc in the hippocampus.
Dr. Richard Palmiter, University of Washington
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.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt the endogenous promoter and exons 1 and 2. The construct was electroporated into 129S7/SvEvBrd derived AB1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to 129S7/SvEvBrd mice before being made homozygous.
|Allele Name||targeted mutation 1, Richard D Palmiter|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Mt3, metallothionein 3|
|Strain of Origin||129S7/SvEvBrd-Hprt+|
|Molecular Note||2.2 kb of sequence, encompassing the promoter and exons 1 and 2, was replaced by a neomycin selection cassette. Quantitative solution hybridization showed an absence of transcript in samples derived from homozygous mutant mice.|
|Mutations Made By|| |
Grant Miura, New York University
When maintaining a live colony, these mice can be bred as homozygotes.
When using the MT-III KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004649 in your Materials and Methods section.