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Gene Review

Mt3  -  metallothionein 3

Mus musculus

Synonyms: GIF, Growth inhibitory factor, MT-3, MT-III, Metallothionein-3, ...
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Disease relevance of Mt3


Psychiatry related information on Mt3


High impact information on Mt3

  • The antigen-specific GEF enhanced the antibody response, and antigen-specific GIF suppressed the antibody response, both in carrier specific manner [7].
  • Mouse MT-III gene expression appears to be restricted to brain; in addition, it fails to respond to zinc, cadmium, dexamethasone, or bacterial endotoxin in vivo, thereby distinguishing MT-III from other known MTs [8].
  • The MT-III genes are closely linked to the other functional MT genes on human chromosome 16 and mouse chromosome 8 [8].
  • Electrophoretic mobility shift assays demonstrate that Egr-1 is involved in the TKE complex that binds to the MT3 element and that expression of Egr-1 induces transcription of a mouse TK-chloramphenicol acetyltransferase reporter in transient transfections [9].
  • This is followed by activation of genes involved in metal ion regulation (metallothionein-I, metallothionein-III, ferritin-H, and ferritin-L) at 4 months of age just prior to end-stage disease, perhaps as an adaptive response to the mitochondrial destruction caused by the mutant protein [10].

Biological context of Mt3


Anatomical context of Mt3


Associations of Mt3 with chemical compounds

  • In contrast to CA1, more neuronal death occurred after kainate-induced seizures in CA3 of Mt3-null mice [1].
  • Because of exchange broadening of a large number of the NMR signals from this domain, homology modeling was utilized to calculate models for the beta-domain and suggested that while the backbone fold of the MT-3 beta-domain is identical to MT-1 and 2, the second proline responsible for the activity, Pro9, may show structural heterogeneity [18].
  • Therefore, Cd, Zn, and Dex induced MT-I and -II mRNA but not MT-III mRNA in astrocytes [19].
  • MT-III-deficient mice were more susceptible to seizures induced by kainic acid and subsequently exhibited greater neuron injury in the CA3 field of hippocampus [13].
  • Interestingly, the MT-I inducers, Cd, Dex, ethanol, and KA, down-regulated brain MT-III mRNA levels by approx. 30% [20].

Physical interactions of Mt3


Regulatory relationships of Mt3


Other interactions of Mt3

  • Solution NMR was utilized to determine the structural and dynamic differences of MT-3 from MT-1 and 2 [18].
  • Furthermore, compared with zinc transporter 3 (Znt3)-null mice, Znt3/Mt3 double-null mice exhibited further reductions in neuronal death in CA1 following kainate-induced seizures [1].
  • MT-I and MT-II are expressed in many tissues, including the brain, whereas MT-III is expressed mainly in the central nervous system [24].
  • In contrast, Mt3-null mice showed increased expression of several neurotrophins as well as of the neuronal sprouting factor GAP-43 [14].
  • Coimmunoprecipitation experiments, also conducted on whole mouse brain extract using the anti-mouse MT-3 antibody along with commercially available antibodies against HSP84 and CK, confirmed that these three proteins were in a single protein complex [5].

Analytical, diagnostic and therapeutic context of Mt3


  1. Zinc released from metallothionein-iii may contribute to hippocampal CA1 and thalamic neuronal death following acute brain injury. Lee, J.Y., Kim, J.H., Palmiter, R.D., Koh, J.Y. Exp. Neurol. (2003) [Pubmed]
  2. Changes of metallothionein 1 and 3 mRNA levels with age in brain of senescence-accelerated mice and the effects of acupuncture. Wen, T., Fan, X., Li, M., Han, J., Shi, X., Xing, L. Am. J. Chin. Med. (2006) [Pubmed]
  3. Characterization of cis-acting elements in the promoter of the mouse metallothionein-3 gene. Activation of gene expression during neuronal differentiation of P19 embryonal carcinoma cells. Faraonio, R., Moffatt, P., Larochelle, O., Schipper, H.M., S-Arnaud, R., Séguin, C. Eur. J. Biochem. (2000) [Pubmed]
  4. Production of interleukin-1 beta-like factor with synovial cell growth promoting activity from adult T-cell leukemia cells. Miyasaka, N., Higaki, M., Sato, K., Hashimoto, J., Taniguchi, A., Kohsaka, H., Yamamoto, K., Shichikawa, K., Nishioka, K. J. Autoimmun. (1991) [Pubmed]
  5. Metallothionein-3 is a component of a multiprotein complex in the mouse brain. El Ghazi, I., Martin, B.L., Armitage, I.M. Exp. Biol. Med. (Maywood) (2006) [Pubmed]
  6. Activation of cellular functions in macrophages by venom secretory Asp-49 and Lys-49 phospholipases A(2). Zuliani, J.P., Gutiérrez, J.M., Casais e Silva, L.L., Coccuzzo Sampaio, S., Lomonte, B., Pereira Teixeira, C.d.e. .F. Toxicon (2005) [Pubmed]
  7. IgE-binding factors and regulation of the IgE antibody response. Ishizaka, K. Annu. Rev. Immunol. (1988) [Pubmed]
  8. MT-III, a brain-specific member of the metallothionein gene family. Palmiter, R.D., Findley, S.D., Whitmore, T.E., Durnam, D.M. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  9. The immediate-early gene Egr-1 regulates the activity of the thymidine kinase promoter at the G0-to-G1 transition of the cell cycle. Molnar, G., Crozat, A., Pardee, A.B. Mol. Cell. Biol. (1994) [Pubmed]
  10. Disease mechanisms revealed by transcription profiling in SOD1-G93A transgenic mouse spinal cord. Olsen, M.K., Roberds, S.L., Ellerbrock, B.R., Fleck, T.J., McKinley, D.K., Gurney, M.E. Ann. Neurol. (2001) [Pubmed]
  11. Interrelationships among brain, endocrine and immune response in ageing and successful ageing: role of metallothionein III isoform. Giacconi, R., Cipriano, C., Muzzioli, M., Gasparini, N., Orlando, F., Mocchegiani, E. Mech. Ageing Dev. (2003) [Pubmed]
  12. Radiation exposure does not alter metallothionein III isoform expression in mouse brain. Ono, S.I., Cai, L., Koropatnick, J., Cherian, M.G. Biological trace element research. (2000) [Pubmed]
  13. Disruption of the metallothionein-III gene in mice: analysis of brain zinc, behavior, and neuron vulnerability to metals, aging, and seizures. Erickson, J.C., Hollopeter, G., Thomas, S.A., Froelick, G.J., Palmiter, R.D. J. Neurosci. (1997) [Pubmed]
  14. Role of metallothionein-III following central nervous system damage. Carrasco, J., Penkowa, M., Giralt, M., Camats, J., Molinero, A., Campbell, I.L., Palmiter, R.D., Hidalgo, J. Neurobiol. Dis. (2003) [Pubmed]
  15. Metallothionein (MT)-III: generation of polyclonal antibodies, comparison with MT-I+II in the freeze lesioned rat brain and in a bioassay with astrocytes, and analysis of Alzheimer's disease brains. Carrasco, J., Giralt, M., Molinero, A., Penkowa, M., Moos, T., Hidalgo, J. J. Neurotrauma (1999) [Pubmed]
  16. Activation of the complete mouse metallothionein gene locus in the maternal deciduum. Liang, L., Fu, K., Lee, D.K., Sobieski, R.J., Dalton, T., Andrews, G.K. Mol. Reprod. Dev. (1996) [Pubmed]
  17. Metallothionein III is expressed in neurons that sequester zinc in synaptic vesicles. Masters, B.A., Quaife, C.J., Erickson, J.C., Kelly, E.J., Froelick, G.J., Zambrowicz, B.P., Brinster, R.L., Palmiter, R.D. J. Neurosci. (1994) [Pubmed]
  18. Three-dimensional structure and dynamics of a brain specific growth inhibitory factor: metallothionein-3. Oz, G., Zangger, K., Armitage, I.M. Biochemistry (2001) [Pubmed]
  19. Induction of metallothionein mRNA and protein in murine astrocyte cultures. Kramer, K.K., Liu, J., Choudhuri, S., Klaassen, C.D. Toxicol. Appl. Pharmacol. (1996) [Pubmed]
  20. Chemical modulation of metallothionein I and III mRNA in mouse brain. Zheng, H., Berman, N.E., Klaassen, C.D. Neurochem. Int. (1995) [Pubmed]
  21. Metal components analysis of metallothionein-III in the brain sections of metallothionein-I and metallothionein-II null mice exposed to mercury vapor with HPLC/ICP-MS. Kameo, S., Nakai, K., Kurokawa, N., Kanehisa, T., Naganuma, A., Satoh, H. Analytical and bioanalytical chemistry. (2005) [Pubmed]
  22. Organs from mice deleted for NRH:quinone oxidoreductase 2 are deprived of the melatonin binding site MT3. Mailliet, F., Ferry, G., Vella, F., Thiam, K., Delagrange, P., Boutin, J.A. FEBS Lett. (2004) [Pubmed]
  23. Inflammatory events induced by Lys-49 and Asp-49 phospholipases A2 isolated from Bothrops asper snake venom: role of catalytic activity. Zuliani, J.P., Fernandes, C.M., Zamuner, S.R., Gutiérrez, J.M., Teixeira, C.F. Toxicon (2005) [Pubmed]
  24. Transgenic expression of interleukin 6 in the central nervous system regulates brain metallothionein-I and -III expression in mice. Hernández, J., Molinero, A., Campbell, I.L., Hidalgo, J. Brain Res. Mol. Brain Res. (1997) [Pubmed]
  25. Analysis of metallothionein brain gene expression in relation to ethanol preference in mice using cosegregation and gene knockouts. Loney, K.D., Uddin, R.K., Singh, S.M. Alcohol. Clin. Exp. Res. (2006) [Pubmed]
  26. Localization of metallothionein-I and -III expression in the CNS of transgenic mice with astrocyte-targeted expression of interleukin 6. Carrasco, J., Hernandez, J., Gonzalez, B., Campbell, I.L., Hidalgo, J. Exp. Neurol. (1998) [Pubmed]
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