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Gene Review

Mt1  -  metallothionein 1

Mus musculus

Synonyms: MT-1, MT-I, Metallothionein-1, Metallothionein-I, Mt-1
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Disease relevance of Mt1


Psychiatry related information on Mt1


High impact information on Mt1


Chemical compound and disease context of Mt1


Biological context of Mt1


Anatomical context of Mt1

  • We show that metallothionein-I messenger RNA (mRNA) (mouse) and metallothionein-II mRNA (human) are elevated in mutant fibroblasts [2].
  • Expression of MT-I in visceral endoderm cells was dependent on maternal dietary zinc [20].
  • This nuclear Zn2+ release depends on the presence of MT as shown by the lack of this effect in activated endothelial cells from MT-deficient mice and temporally correlates with nuclear MT translocation [18].
  • In the CD-1 strain, LPS induction of MT gene expression occurred in each of 10 organs examined (liver, kidney, pancreas, intestine, lung, heart, brain, ovary, uterus, and spleen) [21].
  • In the oviduct, MT-I mRNA was not abundant in total RNA, but was detected specifically in the epithelial cells of the isthmus region and was elevated in these cells on D3 and D4 of gestation [13].

Associations of Mt1 with chemical compounds

  • However, comparable dose-response curves in mutant and control cells are generated when mouse metallothionein-I mRNA concentrations are measured in cells exposed to varying concentrations of cadmium or copper (metallothionein inducers) [2].
  • It has been shown that NO exogenously applied via NO donors resulting in nitrosative stress leads to cytoplasmic Zn2+ release from the zinc storing protein metallothionein (MT) and probably other proteins that complex Zn2+ via cysteine thiols [18].
  • Mouse MT-I and MT-II mRNAs are induced to approximately the same extent in vivo in response to cadmium, dexamethasone, or lipopolysaccharide [19].
  • In wild-type mice, MT-like immunoreactivity was increased in the inner retina (GCL and IPL) 12 and 24 hours after NMDA injection [22].
  • 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 [23].

Physical interactions of Mt1

  • From the results of HPLC/ICP-MS analyses, it was concluded that the mercury components of MT-III and high molecular weight metal-binding proteins in the cerebellum of MT-I, II null mice were much higher than those of wild-type mice [24].
  • These results show that a metal regulatory element of the mouse MT-1 gene interacts specifically with a nuclear protein of Mr 108,000 and that this protein is distinct from the transcription factor Sp1 [25].
  • Specific antibodies to MT-2 were purified from our antiserum by affinity purification using CH-Sepharose 4B coupled with rat liver MT-1 [26].
  • Conversely, the entire MT4 and both of its domains showed better Cu(I) binding properties than MT1, affording Cu(10)-MT4, Cu(5)-alphaMT4 and Cu(7)-betaMT4, stoichiometries that make the domain dependence toward Cu(I) clear [27].
  • Putative zinc-sensing zinc fingers of metal-response element-binding transcription factor-1 stabilize a metal-dependent chromatin complex on the endogenous metallothionein-I promoter [28].

Co-localisations of Mt1


Regulatory relationships of Mt1


Other interactions of Mt1


Analytical, diagnostic and therapeutic context of Mt1


  1. Identification and characterization of metallothionein-1 and -2 gene expression in the context of (+/-)3,4-methylenedioxymethamphetamine-induced toxicity to brain dopaminergic neurons. Xie, T., Tong, L., McCann, U.D., Yuan, J., Becker, K.G., Mechan, A.O., Cheadle, C., Donovan, D.M., Ricaurte, G.A. J. Neurosci. (2004) [Pubmed]
  2. Metallothionein messenger RNA regulation in the mottled mouse and Menkes kinky hair syndrome. Packman, S., Palmiter, R.D., Karin, M., O'Toole, C. J. Clin. Invest. (1987) [Pubmed]
  3. Obesity and hyperleptinemia in metallothionein (-I and -II) null mice. Beattie, J.H., Wood, A.M., Newman, A.M., Bremner, I., Choo, K.H., Michalska, A.E., Duncan, J.S., Trayhurn, P. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  4. Endotoxin-induced inflammation does not cause hepatic zinc accumulation in mice lacking metallothionein gene expression. Philcox, J.C., Coyle, P., Michalska, A., Choo, K.H., Rofe, A.M. Biochem. J. (1995) [Pubmed]
  5. Stimulatory effects of 4-methylcatechol, dopamine and levodopa on the expression of metallothionein-III (GIF) mRNA in immortalized mouse brain glial cells (VR-2g). Aoki, C., Nakanishi, T., Sogawa, N., Ishii, K., Ogawa, N., Takigawa, M., Furuta, H. Brain Res. (1998) [Pubmed]
  6. Defense mechanisms against cadmium toxicity. III. Effects of pretreatment with a small oral dose of cadmium on metallothionein synthesis after a large oral dose of cadmium in mice. Morita, S. Jpn. J. Pharmacol. (1984) [Pubmed]
  7. Behavioral changes in metallothionein-null mice after the cessation of long-term, low-level exposure to mercury vapor. Yoshida, M., Watanabe, C., Kishimoto, M., Yasutake, A., Satoh, M., Sawada, M., Akama, Y. Toxicol. Lett. (2006) [Pubmed]
  8. Inhibitory mechanisms of metallothionein on platelet aggregation in in vitro and platelet plug formation in in vivo experiments. Sheu, J.R., Hsiao, G., Shen, M.Y., Wang, Y., Lin, K.H., Lin, C.H., Chou, D.S. Exp. Biol. Med. (Maywood) (2003) [Pubmed]
  9. A murine model of Menkes disease reveals a physiological function of metallothionein. Kelly, E.J., Palmiter, R.D. Nat. Genet. (1996) [Pubmed]
  10. Overexpression of TGF alpha in transgenic mice: induction of epithelial hyperplasia, pancreatic metaplasia, and carcinoma of the breast. Sandgren, E.P., Luetteke, N.C., Palmiter, R.D., Brinster, R.L., Lee, D.C. Cell (1990) [Pubmed]
  11. Neuron-specific alternative RNA processing in transgenic mice expressing a metallothionein-calcitonin fusion gene. Crenshaw, E.B., Russo, A.F., Swanson, L.W., Rosenfeld, M.G. Cell (1987) [Pubmed]
  12. Tissue-specific posttranslational processing of pre-prosomatostatin encoded by a metallothionein-somatostatin fusion gene in transgenic mice. Low, M.J., Hammer, R.E., Goodman, R.H., Habener, J.F., Palmiter, R.D., Brinster, R.L. Cell (1985) [Pubmed]
  13. Metallothionein gene expression and metal regulation during preimplantation mouse embryo development (MT mRNA during early development). Andrews, G.K., Huet-Hudson, Y.M., Paria, B.C., McMaster, M.T., De, S.K., Dey, S.K. Dev. Biol. (1991) [Pubmed]
  14. Cytoprotection by metallothionein against gastroduodenal mucosal injury caused by ethanol in mice. Takano, H., Satoh, M., Shimada, A., Sagai, M., Yoshikawa, T., Tohyama, C. Lab. Invest. (2000) [Pubmed]
  15. Retrovirally expressed metal response element-binding transcription factor-1 normalizes metallothionein-1 gene expression and protects cells against zinc, but not cadmium, toxicity. Solis, W.A., Childs, N.L., Weedon, M.N., He, L., Nebert, D.W., Dalton, T.P. Toxicol. Appl. Pharmacol. (2002) [Pubmed]
  16. Metallothionein-mediated neuroprotection in genetically engineered mouse models of Parkinson's disease. Ebadi, M., Brown-Borg, H., El Refaey, H., Singh, B.B., Garrett, S., Shavali, S., Sharma, S.K. Brain Res. Mol. Brain Res. (2005) [Pubmed]
  17. Metallothionein mRNA stability in chicken and mouse cells. De, S.K., Enders, G.C., Andrews, G.K. Biochim. Biophys. Acta (1991) [Pubmed]
  18. Regulation of zinc homeostasis by inducible NO synthase-derived NO: nuclear metallothionein translocation and intranuclear Zn2+ release. Spahl, D.U., Berendji-Grün, D., Suschek, C.V., Kolb-Bachofen, V., Kröncke, K.D. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  19. Regulation, linkage, and sequence of mouse metallothionein I and II genes. Searle, P.F., Davison, B.L., Stuart, G.W., Wilkie, T.M., Norstedt, G., Palmiter, R.D. Mol. Cell. Biol. (1984) [Pubmed]
  20. The transcription factors MTF-1 and USF1 cooperate to regulate mouse metallothionein-I expression in response to the essential metal zinc in visceral endoderm cells during early development. Andrews, G.K., Lee, D.K., Ravindra, R., Lichtlen, P., Sirito, M., Sawadogo, M., Schaffner, W. EMBO J. (2001) [Pubmed]
  21. Endotoxin induction of murine metallothionein gene expression. De, S.K., McMaster, M.T., Andrews, G.K. J. Biol. Chem. (1990) [Pubmed]
  22. Metallothionein, an endogenous antioxidant, protects against retinal neuron damage in mice. Suemori, S., Shimazawa, M., Kawase, K., Satoh, M., Nagase, H., Yamamoto, T., Hara, H. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  23. Three-dimensional structure and dynamics of a brain specific growth inhibitory factor: metallothionein-3. Oz, G., Zangger, K., Armitage, I.M. Biochemistry (2001) [Pubmed]
  24. 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]
  25. Detection of a nuclear protein that interacts with a metal regulatory element of the mouse metallothionein 1 gene. Séguin, C., Prévost, J. Nucleic Acids Res. (1988) [Pubmed]
  26. Heterogeneity of antibodies to metallothionein isomers and development of a simple enzyme-linked immunosorbent assay. Chan, H.M., Pringle, G.A., Cherian, M.G. J. Biochem. Toxicol. (1992) [Pubmed]
  27. Functional differentiation in the mammalian metallothionein gene family: metal binding features of mouse MT4 and comparison with its paralog MT1. Tío, L., Villarreal, L., Atrian, S., Capdevila, M. J. Biol. Chem. (2004) [Pubmed]
  28. Putative zinc-sensing zinc fingers of metal-response element-binding transcription factor-1 stabilize a metal-dependent chromatin complex on the endogenous metallothionein-I promoter. Jiang, H., Daniels, P.J., Andrews, G.K. J. Biol. Chem. (2003) [Pubmed]
  29. Chemical modulation of metallothionein I and III mRNA in mouse brain. Zheng, H., Berman, N.E., Klaassen, C.D. Neurochem. Int. (1995) [Pubmed]
  30. 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]
  31. Abrogation of nuclear factor-kappaB activation is involved in zinc inhibition of lipopolysaccharide-induced tumor necrosis factor-alpha production and liver injury. Zhou, Z., Wang, L., Song, Z., Saari, J.T., McClain, C.J., Kang, Y.J. Am. J. Pathol. (2004) [Pubmed]
  32. Nuclear factor-1 and metal transcription factor-1 synergistically activate the mouse metallothionein-1 gene in response to metal ions. LaRochelle, O., Labbé, S., Harrisson, J.F., Simard, C., Tremblay, V., St-Gelais, G., Govindan, M.V., Séguin, C. J. Biol. Chem. (2008) [Pubmed]
  33. Metallothionein-I overexpression decreases brain pathology in transgenic mice with astrocyte-targeted expression of interleukin-6. Molinero, A., Penkowa, M., Hernández, J., Camats, J., Giralt, M., Lago, N., Carrasco, J., Campbell, I.L., Hidalgo, J. J. Neuropathol. Exp. Neurol. (2003) [Pubmed]
  34. Metallothionein knockout and transgenic mice exhibit altered intestinal processing of zinc with uniform zinc-dependent zinc transporter-1 expression. Davis, S.R., McMahon, R.J., Cousins, R.J. J. Nutr. (1998) [Pubmed]
  35. 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]
  36. Enhanced seizures and hippocampal neurodegeneration following kainic acid-induced seizures in metallothionein-I + II-deficient mice. Carrasco, J., Penkowa, M., Hadberg, H., Molinero, A., Hidalgo, J. Eur. J. Neurosci. (2000) [Pubmed]
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