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Gene Review

Mt2  -  metallothionein 2

Mus musculus

Synonyms: AA409533, MT-2, MT-II, Metallothionein-2, Metallothionein-II, ...
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Disease relevance of Mt2

  • Of 15,000 mouse cDNA fragments studied, metallothionein (Mt)-1 and Mt2 emerged as candidate genes possibly involved in MDMA-induced toxicity to DA neurons [1].
  • Targeted disruption of MT-I and MT-II genes seems to induce moderate obesity, providing a new obese animal model [2].
  • These results have demonstrated that MT-I and MT-II can be induced robustly in the liver and lung following experimental influenza virus infection by overlapping but distinct molecular mechanisms [3].
  • To improve our understanding of the role of MT in epidermal hyperplasia, mice with null mutations in their MT-1 and MT-2 genes were used in this study [4].
  • As expected, MT-I and MT-II immunostaining was dramatically increased in cells surrounding the plaques, consistent with astrocytosis and microgliosis, as well as the increased oxidative stress elicited by the amyloid deposits [5].

Psychiatry related information on Mt2


High impact information on Mt2


Chemical compound and disease context of Mt2

  • Collectively, these results indicate that MDMA-induced toxicity to DA neurons is associated with increased Mt1 and Mt2 gene transcription and translation, possibly as part of a neuroprotective mechanism [1].
  • The in vivo stability of representatives of the four classes of plant MT proteins and a mouse MT2 control expressed in E. coli were enhanced by cadmium (Cd) [11].
  • The regrowth delay of a transplanted syngeneic mouse mammary carcinoma designated MT2 was used to estimate the effects of three-fold combination treatments: X-irradiation; hyperthermia and radiosensitizer; and misonidazole (Ro-07-0582) [12].
  • MTII delivered four times daily by intraperitoneal injection to C57BL/6J mice produced a dose-responsive effect on food intake, body weight, leptin, corticosterone, insulin, and free fatty acids [13].
  • AIMS/HYPOTHESIS: The present study was conducted to evaluate the effects of central administration of melanotan II (MTII), a melanocortin-3/4 receptor agonist, on hepatic and whole-body insulin sensitivity, independent of food intake and body weight [14].

Biological context of Mt2

  • Northern blot analysis confirmed the microarray findings and revealed a dynamic upregulation of Mt1 and Mt2 mRNA in the ventral midbrain within 4-12 hr after MDMA treatment [1].
  • Mice of mixed 129/Ola and C57BL/6J background with targeted disruption of MT-I and MT-II genes are more sensitive to toxic metals and oxidative stress [2].
  • There are four blocks of conserved sequences in the promoters of mouse MT-I, mouse MT-II, and human MT-IIA genes; one includes the TATAAA sequence, and another has been implicated in regulation by heavy metals [10].
  • A comparison of the sequences of mouse MT-I and MT-II genes (as well as those of other mammals) reveals that the coding regions are highly conserved even at "silent" positions but that the noncoding regions and introns are extremely divergent between primates and rodents [10].
  • RNA from preimplantation mouse embryos at different stages of development (Days 1 through 4 of gestation; D1 = vaginal plug) was analyzed using the reverse transcriptase-polymerase chain reaction (RT-PCR) to specifically amplify MT-I and MT-II mRNA transcripts [15].

Anatomical context of Mt2


Associations of Mt2 with chemical compounds

  • Mouse MT-I and MT-II mRNAs are induced to approximately the same extent in vivo in response to cadmium, dexamethasone, or lipopolysaccharide [10].
  • RESULTS: In wild-type mice, MT-II mRNA expression was time-dependently elevated by NMDA (5.9 and 7.4 times versus the nontreated control at 4 and 12 hours, respectively, after injection), with the normal level being regained within 24 hours [20].
  • We have previously reported 1 isoform, MT-II, as a possible candidate gene for ethanol (EtOH) preference (EP) determination in mice [21].
  • Nicotine treatment, which can improve working memory, eliminated the impairment associated with the deletion of the MT-1 and MT-2 genes in a dose-related fashion after acquisition training in the aging adult mice [22].
  • Distribution profiles of metals in the soluble fraction of the liver of CeCl3-treated mice analyzed by high performance liquid chromatography/inductively coupled argon plasma-mass spectrometry (HPLC/ICP-MS) demonstrated that the metal bound to MT-I and MT-II was zinc, but not cerium [23].

Physical interactions of Mt2

  • Specific antibodies to MT-2 were purified from our antiserum by affinity purification using CH-Sepharose 4B coupled with rat liver MT-1 [24].

Regulatory relationships of Mt2


Other interactions of Mt2


Analytical, diagnostic and therapeutic context of Mt2


  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. 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]
  3. Influenza virus infection induces metallothionein gene expression in the mouse liver and lung by overlapping but distinct molecular mechanisms. Ghoshal, K., Majumder, S., Zhu, Q., Hunzeker, J., Datta, J., Shah, M., Sheridan, J.F., Jacob, S.T. Mol. Cell. Biol. (2001) [Pubmed]
  4. Epidermal proliferation of the skin in metallothionein-null mice. Hanada, K., Sawamura, D., Hashimoto, I., Kida, K., Naganuma, A. J. Invest. Dermatol. (1998) [Pubmed]
  5. Expression of Metallothionein-I, -II, and -III in Alzheimer Disease and Animal Models of Neuroinflammation. Hidalgo, J., Penkowa, M., Espejo, C., Mart??nez-C??ceres, E.M., Carrasco, J., Quintana, A., Molinero, A., Florit, S., Giralt, M., Ortega-Aznar, A. 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. 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]
  8. A pair of adjacent glucocorticoid response elements regulate expression of two mouse metallothionein genes. Kelly, E.J., Sandgren, E.P., Brinster, R.L., Palmiter, R.D. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  9. A collection of mRNA species that are inducible in the RAW 264.7 mouse macrophage cell line by gamma interferon and other agents. Farber, J.M. Mol. Cell. Biol. (1992) [Pubmed]
  10. 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]
  11. The plant MT1 metallothioneins are stabilized by binding cadmiums and are required for cadmium tolerance and accumulation. Zimeri, A.M., Dhankher, O.P., McCaig, B., Meagher, R.B. Plant Mol. Biol. (2005) [Pubmed]
  12. Enhancement of radioresponse of a mouse mammary carcinoma to combined treatments with hyperthermia and radiosensitizer misonidazole. Goldfeder, A., Brown, D.M., Berger, A. Cancer Res. (1979) [Pubmed]
  13. Effects of acute and chronic administration of the melanocortin agonist MTII in mice with diet-induced obesity. Pierroz, D.D., Ziotopoulou, M., Ungsunan, L., Moschos, S., Flier, J.S., Mantzoros, C.S. Diabetes (2002) [Pubmed]
  14. Intracerebroventricular administration of melanotan II increases insulin sensitivity of glucose disposal in mice. Heijboer, A.C., van den Hoek, A.M., Pijl, H., Voshol, P.J., Havekes, L.M., Romijn, J.A., Corssmit, E.P. Diabetologia (2005) [Pubmed]
  15. 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]
  16. 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]
  17. Regional brain distribution of metallothionein, zinc and copper in toxic milk mutant and transgenic mice. Ono, S., Koropatnick, D.J., Cherian, M.G. Toxicology (1997) [Pubmed]
  18. Determination of metallothionein-1/metallothionein-2 ratios in the mouse liver and pancreas by capillary zone electrophoresis using a polyacrylamide-coated capillary at neutral pH. Minami, T., Kubo, K., Ichida, S. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. (2002) [Pubmed]
  19. Foreign metallothionein-I expression by transient transfection in MT-I and MT-II null astrocytes confers increased protection against acute methylmercury cytotoxicity. Yao, C.P., Allen, J.W., Mutkus, L.A., Xu, S.B., Tan, K.H., Aschner, M. Brain Res. (2000) [Pubmed]
  20. 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]
  21. 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]
  22. Metallothionein expression and neurocognitive function in mice. Levin, E.D., Perraut, C., Pollard, N., Freedman, J.H. Physiol. Behav. (2006) [Pubmed]
  23. Induction of hepatic metallothionein by trivalent cerium: role of interleukin 6. Kobayashi, K., Shida, R., Hasegawa, T., Satoh, M., Seko, Y., Tohyama, C., Kuroda, J., Shibata, N., Imura, N., Himeno, S. Biol. Pharm. Bull. (2005) [Pubmed]
  24. 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]
  25. 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]
  26. Gene expression in scrapie. Cloning of a new scrapie-responsive gene and the identification of increased levels of seven other mRNA transcripts. Dandoy-Dron, F., Guillo, F., Benboudjema, L., Deslys, J.P., Lasmézas, C., Dormont, D., Tovey, M.G., Dron, M. J. Biol. Chem. (1998) [Pubmed]
  27. Isolation of a gene sequence induced later by tumor-promoting 12-O-tetradecanoylphorbol-13-acetate in mouse osteoblastic cells (MC3T3-E1) and expressed constitutively in ras-transformed cells. Nose, K., Saito, H., Kuroki, T. Cell Growth Differ. (1990) [Pubmed]
  28. Effects of oncogenes on the resistance to cis-diamminedichloroplatinum(II) and metallothionein gene expression. Yamada-Okabe, T., Yamada-Okabe, H., Kashima, Y., Doi, R. Toxicol. Appl. Pharmacol. (1995) [Pubmed]
  29. Metallothionein proteins expression, copper and zinc concentrations, and lipid peroxidation level in a rodent model for amyotrophic lateral sclerosis. Tokuda, E., Ono, S., Ishige, K., Naganuma, A., Ito, Y., Suzuki, T. Toxicology (2007) [Pubmed]
  30. Assignment of genes encoding metallothioneins I and II to Chinese hamster chromosome 3: evidence for the role of chromosome rearrangement in gene amplification. Stallings, R.L., Munk, A.C., Longmire, J.L., Hildebrand, C.E., Crawford, B.D. Mol. Cell. Biol. (1984) [Pubmed]
  31. High levels of metallothionein messenger RNAs in male germ cells of the adult mouse. De, S.K., Enders, G.C., Andrews, G.K. Mol. Endocrinol. (1991) [Pubmed]
  32. Characterizations of the unusual dissociation properties of melanotropin peptides from the melanocortin receptor, hMC1R. Haskell-Luevano, C., Miwa, H., Dickinson, C., Hadley, M.E., Hruby, V.J., Yamada, T., Gantz, I. J. Med. Chem. (1996) [Pubmed]
  33. Oleanolic acid protects against cadmium hepatotoxicity by inducing metallothionein. Liu, Y., Kreppel, H., Liu, J., Choudhuri, S., Klaassen, C.D. J. Pharmacol. Exp. Ther. (1993) [Pubmed]
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