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

• It is concluded that, at non-cytotoxic concentrations, MT-II and MT-III activate defense mechanisms in macrophages up regulating phagocytosis, mainly via mannose and beta-glucan receptors, and the respiratory burst [6].

High impact information on Mt2

• Furthermore, when mutant and control cells are grown to achieve overlapping intracellular copper concentrations in the two cell types, metallothionein-I (mouse) and metallothionein-II (human) mRNA levels are proportional to the intracellular copper concentrations [7].
• Synthesis of mouse metallothionein (MT)-I and MT-II is transcriptionally induced by the synthetic glucocorticoid, dexamethasone (DEX) or both in vivo as well as in numerous cell lines [8].
• Treatment of the animals with RU-486, a glucocorticoid receptor antagonist, inhibited induction of MT-I/MT-II in both liver and lung, revealing a direct role of glucocorticoid that is increased upon infection in this induction process [3].
• CRG-6 corresponds to a new member of a family of interferon-inducible genes clustered on mouse chromosome 1, CRG-9 corresponds to a prostaglandin synthase homolog, CRG-8 corresponds to beta 2-microglobulin, and CRG-4 corresponds to metallothionein II [9].
• Mouse MT-I and MT-II genes are regulated by metals but not by glucocorticoids after transfection into HeLa cells [10].

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

• We show that metallothionein-I messenger RNA (mRNA) (mouse) and metallothionein-II mRNA (human) are elevated in mutant fibroblasts [7].
• MT-I and MT-II are expressed in many tissues, including the brain, whereas MT-III is expressed mainly in the central nervous system [16].
• In control, MT-I/MT-II null, and male MT-I* mice, the hippocampus accumulated the highest level of copper [17].
• Twenty-four hours after the injection, the ratio of MT-1/MT-2 was 0.80+/-0.12 and 1.19+/-0.21 (mean+/-SD) in nuclear and cytosol fractions, respectively [18].
• MT proteins in MT-I and MT-II null astrocytes were undetectable [19].

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

• MT-III induced a larger neutrophil infiltrate than MT-II [25].

Other interactions of Mt2

• In the pancreas, both isoforms were detected in the control mice and the ratio of MT-1/MT-2 was below 1 [18].
• Increased expression of the three remaining genes, beta2 microglobulin, F4/80, and metallothionein II, has previously been reported to occur in experimental scrapie [26].
• In contrast, the level of ScRG-2, apolipoprotein D, and metallothionein II mRNA was only increased at the terminal stage of the disease [26].
• Sequencing showed that three of them (OTS-1, -3, and -4) were those of the metallothionein II gene, and one (OTS-5) was identical to the osteopontin/2ar gene [27].
• This result was coincident with that of reverse transcription polymerase chain reaction that metal-induced MT I mRNA was only detected in the sis- or the ras-transformed cells, whereas any of these oncogenes did not affect the metal-induced transcription of the MT II gene [28].

Analytical, diagnostic and therapeutic context of Mt2

• The expression of MT-I and MT-II (MT-I/II) isoforms were measured together with Western blotting, copper level, and lipid peroxides amounts increased in an age-dependent manner in the spinal cord, the region responsible for motor paralysis [29].
• Southern blot analyses of DNAs isolated from a panel of Chinese hamster X mouse somatic cell hybrids which segregate hamster chromosomes confirmed that both MTI and MTII are located on chromosome 3 [30].
• Northern blotting, in situ hybridization, and oligodeoxyribonucleotide excess solution hybridization were used to quantitate metallothionein-I (MT-I) and MT-II mRNAs in mouse testes [31].
• The prolonged binding, biological activities, and enzymatic stability of MT-I and MT-II make them putative candidates for clinical uses such as external scintigraphy for the localization of tumors (i.e., melanoma) [32].
• Furthermore, OA increased both hepatic MT-I and MT-II levels, as determined by high-performance liquid chromatography/atomic absorption spectrophotometry [33].

References