Gene Symbol: Mt1
Description: metallothionein 1
Alias: MT-I, Mt-1, metallothionein-1, metallothionein-I
Species: mouse
Products:     Mt1

Top Publications

  1. Zhou Z, Wang L, Song Z, Saari J, McClain C, Kang Y. Abrogation of nuclear factor-kappaB activation is involved in zinc inhibition of lipopolysaccharide-induced tumor necrosis factor-alpha production and liver injury. Am J Pathol. 2004;164:1547-56 pubmed
    ..Thus, zinc may be beneficial in the treatment of LPS-induced liver injuries, such as sepsis and alcoholism. ..
  2. Leung Y, Pankhurst M, Dunlop S, Ray S, Dittmann J, Eaton E, et al. Metallothionein induces a regenerative reactive astrocyte phenotype via JAK/STAT and RhoA signalling pathways. Exp Neurol. 2010;221:98-106 pubmed publisher
    ..The results suggest that MT has an important role in mediating permissive astrocytic responses to traumatic brain injury. ..
  3. Carrasco J, Penkowa M, Giralt M, Camats J, Molinero A, Campbell I, et al. Role of metallothionein-III following central nervous system damage. Neurobiol Dis. 2003;13:22-36 pubmed
    ..Mt3-null mice did not differ from control mice in these responses, in sharp contrast to results obtained in Mt1- Mt2-null mice...
  4. Giralt M, Penkowa M, Lago N, Molinero A, Hidalgo J. Metallothionein-1+2 protect the CNS after a focal brain injury. Exp Neurol. 2002;173:114-28 pubmed
    ..These results fully support the notion that MT-1+2 are essential in the CNS for coping with focal brain injury and suggest a potential therapeutic use of these proteins. ..
  5. Davis S, Samuelson D, Cousins R. Metallothionein expression protects against carbon tetrachloride-induced hepatotoxicity, but overexpression and dietary zinc supplementation provide no further protection in metallothionein transgenic and knockout mice. J Nutr. 2001;131:215-22 pubmed
    ..However, neither metallothionein overexpression nor supplemental dietary zinc provided further protection. ..
  6. Carrasco J, Penkowa M, Hadberg H, Molinero A, Hidalgo J. Enhanced seizures and hippocampal neurodegeneration following kainic acid-induced seizures in metallothionein-I + II-deficient mice. Eur J Neurosci. 2000;12:2311-22 pubmed
  7. Crowthers K, Kline V, Giardina C, Lynes M. Augmented humoral immune function in metallothionein-null mice. Toxicol Appl Pharmacol. 2000;166:161-72 pubmed
    ..In conclusion, we have provided evidence that endogenous metallothionein can modulate the immune response in vivo and that intracellular MT may modulate immune function by regulation of transcription factor activity. ..
  8. Penkowa M, Giralt M, Moos T, Thomsen P, Hernandez J, Hidalgo J. Impaired inflammatory response to glial cell death in genetically metallothionein-I- and -II-deficient mice. Exp Neurol. 1999;156:149-64 pubmed
    b>Metallothionein I+II (MT-I+II) are acute-phase proteins which are upregulated during pathological conditions in the brain...
  9. Penkowa M, Carrasco J, Giralt M, Moos T, Hidalgo J. CNS wound healing is severely depressed in metallothionein I- and II-deficient mice. J Neurosci. 1999;19:2535-45 pubmed
    ..Our results demonstrate that MT-I+II are essential for a normal wound repair in the CNS, and that their deficiency impairs neuronal survival. ..

More Information


  1. Rofe A, Philcox J, Coyle P. Trace metal, acute phase and metabolic response to endotoxin in metallothionein-null mice. Biochem J. 1996;314 ( Pt 3):793-7 pubmed
  2. Majumder S, Kutay H, Datta J, Summers D, Jacob S, Ghoshal K. Epigenetic regulation of metallothionein-i gene expression: differential regulation of methylated and unmethylated promoters by DNA methyltransferases and methyl CpG binding proteins. J Cell Biochem. 2006;97:1300-16 pubmed
    ..These studies suggest that the components of epigenetic machinery differentially regulate methylated and unmethylated MT-I gene expression. ..
  3. Spahl D, Berendji Grün D, Suschek C, Kolb Bachofen V, Kröncke K. Regulation of zinc homeostasis by inducible NO synthase-derived NO: nuclear metallothionein translocation and intranuclear Zn2+ release. Proc Natl Acad Sci U S A. 2003;100:13952-7 pubmed
    ..In conclusion, we here provide evidence for a signaling mechanism based on iNOS-derived NO through the regulation of intracellular Zn2+ trafficking and homeostasis. ..
  4. Kimura T, Itoh N, Takehara M, Oguro I, Ishizaki J, Nakanishi T, et al. Sensitivity of metallothionein-null mice to LPS/D-galactosamine-induced lethality. Biochem Biophys Res Commun. 2001;280:358-62 pubmed
    ..These results indicated that MT may have the potential to prevent LPS/GalN-induced lethality, at least through the attenuation of AGP induction. ..
  5. Suemori S, Shimazawa M, Kawase K, Satoh M, Nagase H, Yamamoto T, et al. Metallothionein, an endogenous antioxidant, protects against retinal neuron damage in mice. Invest Ophthalmol Vis Sci. 2006;47:3975-82 pubmed
  6. Liu J, Liu Y, Hartley D, Klaassen C, Shehin Johnson S, Lucas A, et al. Metallothionein-I/II knockout mice are sensitive to acetaminophen-induced hepatotoxicity. J Pharmacol Exp Ther. 1999;289:580-6 pubmed
    ..The increased sensitivity does not appear to be due to increased acetaminophen activation, glutathione depletion, or covalent binding, but appears to be associated with the antioxidant role of MT. ..
  7. Lee D, Carrasco J, Hidalgo J, Andrews G. Identification of a signal transducer and activator of transcription (STAT) binding site in the mouse metallothionein-I promoter involved in interleukin-6-induced gene expression. Biochem J. 1999;337 ( Pt 1):59-65 pubmed
    ..This study suggests that the effects of LPS on hepatic MT-I gene expression are mediated by IL-6 and involve the activation of STAT-binding to the proximal promoter. ..
  8. Masters B, Kelly E, Quaife C, Brinster R, Palmiter R. Targeted disruption of metallothionein I and II genes increases sensitivity to cadmium. Proc Natl Acad Sci U S A. 1994;91:584-8 pubmed
    ..This proves that these widely expressed MTs are not essential for development but that they do protect against cadmium toxicity. These mice provide a means for testing other proposed functions of MT in vivo. ..
  9. Philcox J, Coyle P, Michalska A, Choo K, Rofe A. Endotoxin-induced inflammation does not cause hepatic zinc accumulation in mice lacking metallothionein gene expression. Biochem J. 1995;308 ( Pt 2):543-6 pubmed
    ..This study confirms that MT synthesis is essential for endotoxin-induced liver Zn accumulation. ..
  10. Michalska A, Choo K. Targeting and germ-line transmission of a null mutation at the metallothionein I and II loci in mouse. Proc Natl Acad Sci U S A. 1993;90:8088-92 pubmed
    ..These mice should provide a useful model to allow detailed study of the physiological roles of MT-I and MT-II. ..
  11. Oshima Y, Fujio Y, Nakanishi T, Itoh N, Yamamoto Y, Negoro S, et al. STAT3 mediates cardioprotection against ischemia/reperfusion injury through metallothionein induction in the heart. Cardiovasc Res. 2005;65:428-35 pubmed
    ..In parallel, ROS scavengers, metallothionein1 (MT1), and metallothionein2 (MT2) were markedly up-regulated in TG hearts...
  12. Conrad C, Grabowski D, Walter C, Sabia M, Richardson A. Using MT(-/-) mice to study metallothionein and oxidative stress. Free Radic Biol Med. 2000;28:447-62 pubmed
    ..However, the mean survival increased significantly after zinc pretreatment for both the MT(-/-) and MT(+/+) mice. These results demonstrate that tissue levels of metallothionein do not protect mice in vivo against oxidative stress. ..
  13. Wu C, Pot C, Apetoh L, Thalhamer T, Zhu B, Murugaiyan G, et al. Metallothioneins negatively regulate IL-27-induced type 1 regulatory T-cell differentiation. Proc Natl Acad Sci U S A. 2013;110:7802-7 pubmed publisher
    ..Moreover, activation of STAT1 and/or STAT3 can overcome the suppression of IL-10 by MTs, indicating a dynamic balance between STATs and MTs in regulating IL-10 during Tr1 cell differentiation. ..
  14. Kelly E, Quaife C, Froelick G, Palmiter R. Metallothionein I and II protect against zinc deficiency and zinc toxicity in mice. J Nutr. 1996;126:1782-90 pubmed
    ..To examine the importance of MT for these processes, mice with null alleles of both MT I and MT II genes were created and the zinc concentration and histological appearance of multiple organs assessed...
  15. Ono S, Ishizaki Y, Tokuda E, Tabata K, Asami S, Suzuki T. Different patterns in the induction of metallothionein mRNA synthesis among isoforms after acute ethanol administration. Biol Trace Elem Res. 2007;115:147-56 pubmed
    ..On the other hand, the MT-III isoform, which has a limited tissue distribution, especially in the central nervous system, seems to be implicated in tissue repair and/or protection against critical tissue injury. ..
  16. Liu J, Liu Y, Habeebu S, Klaassen C. Metallothionein-null mice are highly susceptible to the hematotoxic and immunotoxic effects of chronic CdCl2 exposure. Toxicol Appl Pharmacol. 1999;159:98-108 pubmed
    ..In conclusion, the present study demonstrates that repeated injections of Cd produces hematotoxic and immunotoxic effects, and intracellular MT protects against these chronic Cd-induced effects. ..
  17. Abe T, Yamamoto O, Gotoh S, Yan Y, Todaka N, Higashi K. Cadmium-induced mRNA expression of Hsp32 is augmented in metallothionein-I and -II knock-out mice. Arch Biochem Biophys. 2000;382:81-8 pubmed
    ..We suggest that organs of low stress response to cadmium such as the testis and lung may be vulnerable target sites for cadmium toxicity and carcinogenesis. ..
  18. Stallings R, Munk A, Longmire J, Hildebrand C, Crawford B. Assignment of genes encoding metallothioneins I and II to Chinese hamster chromosome 3: evidence for the role of chromosome rearrangement in gene amplification. Mol Cell Biol. 1984;4:2932-6 pubmed
    Cadmium resistant (Cdr) variants with coordinately amplified metallothionein I and II (MTI and MTII) genes have been derived from both Chinese hamster ovary and near-euploid Chinese hamster cell lines...
  19. Leazer T, Daston G, Keen C, Rogers J. The embryolethality of lipopolysaccharide in CD-1 and metallothionein I-II null mice: lack of a role for induced zinc deficiency or metallothionein induction. Toxicol Sci. 2003;73:442-7 pubmed
    ..the effects of maternal Zn supplementation on LPS developmental toxicity, and (3) assessing the role of MT with MT I-II null mice (MTKO). Timed pregnant CD-1 mice were dosed i.p. with LPS (S. typhimurium) (0...
  20. Iszard M, Liu J, Liu Y, Dalton T, Andrews G, Palmiter R, et al. Characterization of metallothionein-I-transgenic mice. Toxicol Appl Pharmacol. 1995;133:305-12 pubmed
    ..Thus, MT-TG mice appear to be a good model for studying functions of MT. ..
  21. Xiang J, Koropatnick J, Qi Y, Luo X, Moyana T, Li K, et al. Production of a bifunctional hybrid molecule B72.3/metallothionein-1 by protein engineering. Immunology. 1993;78:574-81 pubmed
    ..3 antibody, and the metal-binding capacity of the native metallothionein molecule. Therefore, the bifunctional hybrid protein B72.3MT-1 may be very useful in cancer imaging when labelled with radionuclides such as 99mTc. ..
  22. Andrews G, Huet Hudson Y, Paria B, McMaster M, De S, Dey S. Metallothionein gene expression and metal regulation during preimplantation mouse embryo development (MT mRNA during early development). Dev Biol. 1991;145:13-27 pubmed
    ..Sensitivity and resistance of preimplantation embryos to acute metal toxicity involve mechanisms other than MT gene expression in preimplantation mouse embryos.(ABSTRACT TRUNCATED AT 400 WORDS) ..
  23. Xu J, Wang G, Wang Y, Liu Q, Xu W, Tan Y, et al. Diabetes- and angiotensin II-induced cardiac endoplasmic reticulum stress and cell death: metallothionein protection. J Cell Mol Med. 2009;13:1499-512 pubmed publisher
    ..MT prevents both diabetes- and Ang II-induced cardiac ER stress and associated cell death most likely via its antioxidant action, which may be responsible for MT's prevention of DCM. ..
  24. Hao Y, Huang J, Gu Y, Liu C, Li H, Liu J, et al. Metallothionein deficiency aggravates depleted uranium-induced nephrotoxicity. Toxicol Appl Pharmacol. 2015;287:306-15 pubmed publisher
    ..In conclusion, MT deficiency aggravated DU-induced nephrotoxicity, and the molecular mechanisms appeared to be related to the increased oxidative stress and apoptosis, and decreased SGLT expression. ..
  25. Xu C. cDNA cloning of a mouse factor that activates transcription from a metal response element of the mouse metallothionein-I gene in yeast. DNA Cell Biol. 1993;12:517-25 pubmed
    ..The cDNA hybridizes to a 550-base mRNA that is constitutively expressed in mouse tissue culture cells. The ability of the mouse factor to activate transcription in yeast cells is dependent upon the carbon source. ..
  26. Choudhuri S, McKim J, Klaassen C. Differential expression of the metallothionein gene in liver and brain of mice and rats. Toxicol Appl Pharmacol. 1993;119:1-10 pubmed
    Expression of the metallothionein I (MT-I) gene was studied in liver and brain of control mice and rats, as well as following administration of Cd and lipopolysaccharide (LPS)...
  27. Skabo S, Holloway A, West A, Chuah M. Metallothioneins 1 and 2 are expressed in the olfactory mucosa of mice in untreated animals and during the regeneration of the epithelial layer. Biochem Biophys Res Commun. 1997;232:136-42 pubmed
    We have examined the expression of the MT1 and MT2 isoforms of metallothionein in the mouse olfactory mucosa...
  28. Ebadi M, Sharma S. Metallothioneins 1 and 2 attenuate peroxynitrite-induced oxidative stress in Parkinson disease. Exp Biol Med (Maywood). 2006;231:1576-83 pubmed
    ..These observations provide further evidence that nitric oxide synthase activation and ONOO- synthesis may be involved in the etiopathogenesis of PD, and that metallothionein gene induction may provide neuroprotection. ..
  29. Beltramini M, Di Pisa C, Zambenedetti P, Wittkowski W, Mocchegiani E, Musicco M, et al. Zn and Cu alteration in connection with astrocyte metallothionein I/II overexpression in the mouse brain upon physical stress. Glia. 2004;47:30-4 pubmed
    ..b>Metallothionein I/II expression was compared with the immunopositivity of glial fibrillary acidic protein (GFAP)...
  30. Liu J, Liu Y, Michalska A, Choo K, Klaassen C. Distribution and retention of cadmium in metallothionein I and II null mice. Toxicol Appl Pharmacol. 1996;136:260-8 pubmed
    ..These data support the conclusion that the persistence of Cd in the body is at least partially due to Cd binding to MT in tissues. ..
  31. Vorbrodt A, Dobrogowska D, Meeker H, Carp R. Quantitative immunogold study of increased expression of metallothionein-I/II in the brain perivascular areas of diabetic scrapie-infected mice. J Mol Histol. 2006;37:143-51 pubmed
    Quantitative immunogold procedure was used to study the distribution of metallothionein I/II (MT-I/II) at the ultrastructural level in the perivascular areas, including microvascular endothelial cells (ECs) and astrocytes with their ..
  32. Dufner Beattie J, Langmade S, Wang F, Eide D, Andrews G. Structure, function, and regulation of a subfamily of mouse zinc transporter genes. J Biol Chem. 2003;278:50142-50 pubmed
    ..very rare or moderately rare, respectively, and tissue-restricted in their accumulation; and 2) unlike mouse metallothionein I and zip4 mRNAs (Dufner-Beattie, J., Wang, F., Kuo, Y.-M., Gitschier, J., Eide, D., and Andrews, G. K...
  33. Sato M, Kawakami T, Kondoh M, Takiguchi M, Kadota Y, Himeno S, et al. Development of high-fat-diet-induced obesity in female metallothionein-null mice. FASEB J. 2010;24:2375-84 pubmed publisher
    ..Thus, MT may have a preventive role against HFD-induced obesity by regulating adipocyte enlargement and leptin signaling. ..
  34. Searle P, Davison B, Stuart G, Wilkie T, Norstedt G, Palmiter R. Regulation, linkage, and sequence of mouse metallothionein I and II genes. Mol Cell Biol. 1984;4:1221-30 pubmed
    ..Mouse MT-I and MT-II genes are regulated by metals but not by glucocorticoids after transfection into HeLa cells. ..
  35. Lian Y, Zhao J, Xu P, Wang Y, Zhao J, Jia L, et al. Protective effects of metallothionein on isoniazid and rifampicin-induced hepatotoxicity in mice. PLoS ONE. 2013;8:e72058 pubmed publisher
    ..These findings clearly demonstrate that basal MT provides protection against INH and RFP-induced toxicity in hepatocytes. The CYP2E1 and CYP1A2 were involved in the pathogenesis of INH and RFP-induced hepatotoxicity. ..
  36. Tsuji T, Naito Y, Takagi T, Kugai M, Yoriki H, Horie R, et al. Role of metallothionein in murine experimental colitis. Int J Mol Med. 2013;31:1037-46 pubmed publisher
    ..These data indicate that MTs play an important role in the prevention of colonic mucosal inflammation in a mouse model of DSS-induced colitis, thus suggesting that endogenous MTs play a protective role against intestinal inflammation. ..
  37. Kimura T, Okumura F, Onodera A, Nakanishi T, Itoh N, Isobe M. Chromium (VI) inhibits mouse metallothionein-I gene transcription by modifying the transcription potential of the co-activator p300. J Toxicol Sci. 2011;36:173-80 pubmed
    ..This suggests that the inhibitory effects of Cr(VI) on MT-I transcription may be due to its effects on the HAT-independent transactivation ability rather than the HAT-dependent, HDAC release-related transactivation ability of p300. ..
  38. St Croix C, Wasserloos K, Dineley K, Reynolds I, Levitan E, Pitt B. Nitric oxide-induced changes in intracellular zinc homeostasis are mediated by metallothionein/thionein. Am J Physiol Lung Cell Mol Physiol. 2002;282:L185-92 pubmed
    ..Collectively, these data show that MT mediates NO-induced changes in intracellular Zn(2+) and suggest that the ratio of MT to T can regulate Zn(2+) homeostasis in response to nitrosative stress. ..
  39. Li Q, Hu N, Daggett M, Chu W, Bittel D, Johnson J, et al. Participation of upstream stimulator factor (USF) in cadmium-induction of the mouse metallothionein-I gene. Nucleic Acids Res. 1998;26:5182-9 pubmed
    ..The data further suggest that USF interacts with ARE-binding proteins to influence MT-I gene expression. ..
  40. Stankovic R, Li Z. Decreased neurofilament density in large myelinated axons of metallothionein-I, II knockout mice. Neurosci Lett. 2006;402:1-6 pubmed
    ..005). This observation may have novel therapeutic implications in the treatment of amyotrophic lateral sclerosis (ALS), particularly as the terminal phases of the disease involve respiratory insufficiency. ..
  41. Andrews G, Geiser J. Expression of the mouse metallothionein-I and -II genes provides a reproductive advantage during maternal dietary zinc deficiency. J Nutr. 1999;129:1643-8 pubmed
    ..These results demonstrate that the expression of the MT-I and -II genes in pregnant females improves reproductive success during maternal dietary zinc deficiency. ..
  42. Baker Z, Jett K, Boulet A, Hossain A, Cobine P, Kim B, et al. The mitochondrial metallochaperone SCO1 maintains CTR1 at the plasma membrane to preserve copper homeostasis in the murine heart. Hum Mol Genet. 2017;26:4617-4628 pubmed publisher
  43. Yang H, Wang Y, Peng S. Metallothionein-I/II null cardiomyocytes are sensitive to Fusarium mycotoxin butenolide-induced cytotoxicity and oxidative DNA damage. Toxicon. 2010;55:1291-6 pubmed publisher
    ..Taken together, these findings clearly show that basal MT can efficiently attenuate BUT-induced cytotoxic injuries in cardiomyocytes via the inhibition of intracellular ROS production, and associated DNA damage. ..
  44. Chen S, Han J, Liu Y. Dual Opposing Roles of Metallothionein Overexpression in C57BL/6J Mouse Pancreatic β-Cells. PLoS ONE. 2015;10:e0137583 pubmed publisher
    ..MT overexpression protected β-cells from acute STZ-induced ROS damages at young age, whereas it impaired GSIS and promoted the development of diabetes in adult C57BL/6J mice, and more severe damage was found in males. ..
  45. Waalkes M, Liu J, Kasprzak K, Diwan B. Metallothionein-I/II double knockout mice are no more sensitive to the carcinogenic effects of nickel subsulfide than wild-type mice. Int J Toxicol. 2005;24:215-20 pubmed
    ..Overall, MT-null mice appear no more sensitive to the carcinogenic effects of nickel than WT mice. Thus, poor MT production does not appear to be a predisposing factor for nickel carcinogenesis. ..
  46. Kennette W, Collins O, Zalups R, Koropatnick J. Basal and zinc-induced metallothionein in resistance to cadmium, cisplatin, zinc, and tertbutyl hydroperoxide: studies using MT knockout and antisense-downregulated MT in mammalian cells. Toxicol Sci. 2005;88:602-13 pubmed
    ..Moreover, resistance to some agents (Cd and CDDP) can be enhanced by inducing MT. Resistance to other agents (tBH) requires only basal (non-induced) MT levels. ..
  47. Freudenberg J, Chen W. Induction of Smad1 by MT1-MMP contributes to tumor growth. Int J Cancer. 2007;121:966-77 pubmed
    b>MT1-MMP is a key integral membrane protease, which regulates tumor growth by cleaving extracellular matrix components, activating growth factors and receptors, and consequently, triggering downstream signals...
  48. Wakida K, Shimazawa M, Hozumi I, Satoh M, Nagase H, Inuzuka T, et al. Neuroprotective effect of erythropoietin, and role of metallothionein-1 and -2, in permanent focal cerebral ischemia. Neuroscience. 2007;148:105-14 pubmed
    ..These findings indicate that MTs are induced, and may be neuroprotective against neuronal damage, after MCAO. Furthermore, EPO is neuroprotective in vivo during permanent MCAO, and this may be at least partly mediated by MTs. ..
  49. Vancura P, Abdelhadi S, Csicsely E, Baba K, Tosini G, Iuvone P, et al. Gnaz couples the circadian and dopaminergic system to G protein-mediated signaling in mouse photoreceptors. PLoS ONE. 2017;12:e0187411 pubmed publisher
    ..the rhythmic release of the neurohormones dopamine-acting on dopamine D4 receptors-and melatonin-acting on MT1 and MT2 receptors...
  50. DeRuisseau L, Recca D, Mogle J, Zoccolillo M, DeRuisseau K. Metallothionein deficiency leads to soleus muscle contractile dysfunction following acute spinal cord injury in mice. Am J Physiol Regul Integr Comp Physiol. 2009;297:R1795-802 pubmed publisher
    ..These findings suggest a role of MT in mediating protective adaptations in skeletal muscle following disuse mediated by spinal cord injury. ..
  51. Yoshida M, Watanabe C, Satoh M, Yasutake A, Sawada M, Ohtsuka Y, et al. Susceptibility of metallothionein-null mice to the behavioral alterations caused by exposure to mercury vapor at human-relevant concentration. Toxicol Sci. 2004;80:69-73 pubmed
  52. Sun X, Zhou Z, Kang Y. Attenuation of doxorubicin chronic toxicity in metallothionein-overexpressing transgenic mouse heart. Cancer Res. 2001;61:3382-7 pubmed
    ..This study also suggests that oxidative stress is critically involved in the DOX-induced chronic cardiotoxicity. ..
  53. Kilic U, Yilmaz B, Ugur M, Yuksel A, Reiter R, Hermann D, et al. Evidence that membrane-bound G protein-coupled melatonin receptors MT1 and MT2 are not involved in the neuroprotective effects of melatonin in focal cerebral ischemia. J Pineal Res. 2012;52:228-35 pubmed publisher
    ..released by the pineal gland in a circadian rhythm, and many of its peripheral actions are mediated via membrane MT1 and MT2 receptors...
  54. Hanada K. Photoprotective role of metallothionein in UV-injury - metallothionein-null mouse exhibits reduced tolerance against ultraviolet-B. J Dermatol Sci. 2000;23 Suppl 1:S51-6 pubmed
    ..These findings indicate that the skin of MT-null mouse is readily injured by UVB irradiation. MT-null mouse provided direct evidence of the photoprotective effect of cellular MTs in the skin. ..
  55. Kondo Y, Himeno S, Endo W, Mita M, Suzuki Y, Nemoto K, et al. Metallothionein modulates the carcinogenicity of N-butyl-N-(4-hydroxybutyl)nitrosamine in mice. Carcinogenesis. 1999;20:1625-7 pubmed
    ..These results indicate that MT is an important modulator of carcinogenicity of BBN in the bladder of mice. ..
  56. Sun W, Miao X, Zhou S, Zhang L, Epstein P, Mellen N, et al. Zinc rescue of Akt2 gene deletion-linked murine cardiac dysfunction and pathological changes is metallothionein-dependent. J Mol Cell Cardiol. 2014;74:88-97 pubmed publisher
    ..The cardioprotective effects of zinc are metallothionein-dependent. This is very important since zinc supplementation may be required for patients with Akt2 gene deficiency or insulin resistance. ..
  57. Bae S, Ogawa E, Maruyama M, Oka H, Satake M, Shigesada K, et al. PEBP2 alpha B/mouse AML1 consists of multiple isoforms that possess differential transactivation potentials. Mol Cell Biol. 1994;14:3242-52 pubmed
    ..These results suggest that previously described chimeric gene products, AML1/MTG8(ETO) and AML1-EAP generated by t(8;21) and t(3;21), respectively, lack the transactivation domain of AML1. ..
  58. Alam J, Smith A. Heme-hemopexin-mediated induction of metallothionein gene expression. J Biol Chem. 1992;267:16379-84 pubmed
  59. Minami T, Miyata E, Sakamoto Y, Kohama A, Yamazaki H, Ichida S. Expression of metallothionein mRNAs on mouse cerebellum microglia cells by thimerosal and its metabolites. Toxicology. 2009;261:25-32 pubmed publisher
    ..The reduction of MT-1 mRNA level by thiosalicylate may affect the proliferation of C8-B4 cells. ..
  60. Inoue K, Takano H, Kaewamatawong T, Shimada A, Suzuki J, Yanagisawa R, et al. Role of metallothionein in lung inflammation induced by ozone exposure in mice. Free Radic Biol Med. 2008;45:1714-22 pubmed publisher
    ..Collectively, MT protects against O(3)-induced lung inflammation, at least partly, via the regulation of pulmonary endothelial and epithelial integrity and its antioxidative property. ..
  61. Nishimura N, Nishimura H, Ghaffar A, Tohyama C. Localization of metallothionein in the brain of rat and mouse. J Histochem Cytochem. 1992;40:309-15 pubmed
    ..The present result suggest a possible link of MT with cell growth of choroid plexus epithelium and ependymal cells, as well as a detoxifying role of MT in the blood-brain barrier and the cerebrospinal fluid-brain barrier. ..
  62. Bernal P, Leelavanichkul K, Bauer E, Cao R, Wilson A, Wasserloos K, et al. Nitric-oxide-mediated zinc release contributes to hypoxic regulation of pulmonary vascular tone. Circ Res. 2008;102:1575-83 pubmed publisher
    ..Collectively, these data suggest that zinc thiolate signaling is a component of the effects of acute hypoxia-mediated NO biosynthesis and that this pathway may contribute to constriction in the pulmonary vasculature. ..
  63. Plisov S, Nichiporenko M, Shkapenko A, Kumarev V, Baranova L, Merkulova T. The immediate vicinity of mouse metallothionein-I gene contains two sites conferring glucocorticoid inducibility to the heterologous promoter. FEBS Lett. 1994;352:339-41 pubmed
    ..However, the promoter region of the mMT-I gene (-330 to +70 bp) was found to provide low, if any, glucocorticoid induction of the linked CAT gene, while showing strong cadmium regulation, comparable with the in vivo level. ..
  64. Leiva Presa A, Capdevila M, González Duarte P. Mercury(II) binding to metallothioneins. Variables governing the formation and structural features of the mammalian Hg-MT species. Eur J Biochem. 2004;271:4872-80 pubmed
  65. Heuchel R, Radtke F, Georgiev O, Stark G, Aguet M, Schaffner W. The transcription factor MTF-1 is essential for basal and heavy metal-induced metallothionein gene expression. EMBO J. 1994;13:2870-5 pubmed
    ..Moreover, due to the loss of MTF-1, the endogenous metallothionein I and II genes are silent, indicating that MTF-1 is required for both their basal and zinc-induced ..
  66. Stankovic R, Lee V, Kekic M, Harper C. The expression and significance of metallothioneins in murine organs and tissues following mercury vapour exposure. Toxicol Pathol. 2003;31:514-23 pubmed
    ..The absence of MT expression in motor neurons and their axons suggests the dependence of the motor system on the detoxifying capacity of liver MTs. ..
  67. Langmade S, Ravindra R, Daniels P, Andrews G. The transcription factor MTF-1 mediates metal regulation of the mouse ZnT1 gene. J Biol Chem. 2000;275:34803-9 pubmed
    ..Changes in ZnT1 gene expression in these experiments paralleled those of metallothionein I (MT-I)...
  68. Scherer G, Bausch E, Gaa A, von Deimling O. Gene mapping on mouse chromosome 8 by interspecific crosses: new data on a linkage group conserved on human chromosome 16q. Genomics. 1989;5:275-82 pubmed
    ..While map distances between HP-TAT,HP-CTRB, and TAT-CTRB of respectively 7, 11, and 9 cM have previously been measured in man, no crossovers between Hp, Tat, and Ctrb were observed in over 100 meioses in the mouse. ..
  69. Di Foggia V, Zhang X, Licastro D, Gerli M, Phadke R, Muntoni F, et al. Bmi1 enhances skeletal muscle regeneration through MT1-mediated oxidative stress protection in a mouse model of dystrophinopathy. J Exp Med. 2014;211:2617-33 pubmed publisher
    ..underlying enhanced physiological function of Bmi1 depends on the injury context and it is mediated by metallothionein 1 (MT1)-driven modulation of resistance to oxidative stress in the satellite cell population...
  70. Gunes C, Heuchel R, Georgiev O, Müller K, Lichtlen P, Blüthmann H, et al. Embryonic lethality and liver degeneration in mice lacking the metal-responsive transcriptional activator MTF-1. EMBO J. 1998;17:2846-54 pubmed
    ..MTF-1(-/-) embryos fail to transcribe metallothionein I and II genes, and also show diminished transcripts of the gene which encodes the heavy-chain subunit of the ..
  71. Carrasco J, Hernandez J, Bluethmann H, Hidalgo J. Interleukin-6 and tumor necrosis factor-alpha type 1 receptor deficient mice reveal a role of IL-6 and TNF-alpha on brain metallothionein-I and -III regulation. Brain Res Mol Brain Res. 1998;57:221-34 pubmed
    ..These results demonstrate that IL-6 and TNF-alpha are involved in brain MTs regulation during LPS-elicited inflammatory response but not during the stress response. ..
  72. Pankhurst M, Bennett W, Kirkcaldie M, West A, Chung R. Increased circulating leukocyte numbers and altered macrophage phenotype correlate with the altered immune response to brain injury in metallothionein (MT)-I/II null mutant mice. J Neuroinflammation. 2011;8:172 pubmed publisher
  73. Smith P, Wiltshire M, Furon E, Beattie J, Errington R. Impact of overexpression of metallothionein-1 on cell cycle progression and zinc toxicity. Am J Physiol Cell Physiol. 2008;295:C1399-408 pubmed publisher
    ..The results have implications for the use of cellular stress responses to exogenously supplied zinc and zinc-based systemic therapies. ..
  74. Levin E, Perraut C, Pollard N, Freedman J. Metallothionein expression and neurocognitive function in mice. Physiol Behav. 2006;87:513-8 pubmed
    ..These results suggest that metallothioneins, through there roles in metal physiology or cellular protection, are involved in spatial learning and memory function. ..
  75. Hashimoto K, Hayashi Y, Inuzuka T, Hozumi I. Exercise induces metallothioneins in mouse spinal cord. Neuroscience. 2009;163:244-51 pubmed publisher
    ..We revealed that regular exercise induced transient increases in the expression levels of MT mRNAs and resulted in accumulation of MT proteins in the spinal cords of the normal mice. ..
  76. Takano H, Satoh M, Shimada A, Sagai M, Yoshikawa T, Tohyama C. Cytoprotection by metallothionein against gastroduodenal mucosal injury caused by ethanol in mice. Lab Invest. 2000;80:371-7 pubmed
    ..These results provide direct evidence that intrinsic MT plays a cytoprotective role in gastroduodenal mucosal injury caused by ethanol. ..
  77. Giralt M, Penkowa M, Hernández J, Molinero A, Carrasco J, Lago N, et al. Metallothionein-1+2 deficiency increases brain pathology in transgenic mice with astrocyte-targeted expression of interleukin 6. Neurobiol Dis. 2002;9:319-38 pubmed
    ..Overall, the results suggest that the MT-1+2 proteins are valuable factors against cytokine-induced CNS injury. ..
  78. Hyldahl R, O Fallon K, Schwartz L, Clarkson P. Knockdown of metallothionein 1 and 2 does not affect atrophy or oxidant activity in a novel in vitro model. J Appl Physiol (1985). 2010;109:1515-23 pubmed publisher
    ..We therefore conclude that the novel SR model results in a strong atrophy response and an increase in oxidant activity in cultured myotubes and that knockdown of MT does not affect that response. ..
  79. Sun W, Wang Y, Miao X, Wang Y, Zhang L, Xin Y, et al. Renal improvement by zinc in diabetic mice is associated with glucose metabolism signaling mediated by metallothionein and Akt, but not Akt2. Free Radic Biol Med. 2014;68:22-34 pubmed publisher
  80. Pathak B, Shaughnessy J, Meneton P, Greeb J, Shull G, Jenkins N, et al. Mouse chromosomal location of three epithelial sodium channel subunit genes and an apical sodium chloride cotransporter gene. Genomics. 1996;33:124-7 pubmed
    ..These loci map to previously defined homologous regions between human and mouse chromosomes and provide additional information regarding human/mouse comparative mapping. ..
  81. Cipriano C, Giacconi R, Muzzioli M, Gasparini N, Orlando F, Corradi A, et al. Metallothionein (I+II) confers, via c-myc, immune plasticity in oldest mice: model of partial hepatectomy/liver regeneration. Mech Ageing Dev. 2003;124:877-86 pubmed
    ..The combination of immune depression and enhanced c-myc, via high MT, may trigger the appearance of age-related degenerative diseases. ..
  82. Tio L, Villarreal L, Atrian S, Capdevila M. Functional differentiation in the mammalian metallothionein gene family: metal binding features of mouse MT4 and comparison with its paralog MT1. J Biol Chem. 2004;279:24403-13 pubmed
    ..characterization of the metal binding abilities of mammalian MT4 and their comparison with those of the well known MT1. Heterologous Escherichia coli expression in cultures supplemented with zinc, cadmium, or copper was achieved for ..
  83. Lichten L, Liuzzi J, Cousins R. Interleukin-1beta contributes via nitric oxide to the upregulation and functional activity of the zinc transporter Zip14 (Slc39a14) in murine hepatocytes. Am J Physiol Gastrointest Liver Physiol. 2009;296:G860-7 pubmed publisher
    ..These data suggest that signaling pathways activated by NO are factors in the upregulation of Zip14, which in turn mediates hepatic zinc accumulation and hypozincemia during inflammation and sepsis. ..