Targeting and germ-line transmission of a null mutation at the metallothionein I and II loci in mouse.

Michalska, Anna; Choo, K. H. Andy

doi:10.1073/pnas.90.17.8088

Cited by 356 publications

(220 citation statements)

References 27 publications

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“…MT-null mice whose MT-I and MT-II genes had null mutations and wild-type mice were kindly provided by Dr. A. Choo (Murdoch Institute for Research into Birth Defects, Royal Children's Hospital, Parkville, Australia) (Michalska and Choo, 1993). Both kinds of mice were originally from a mixed genetic background of OLA129 and C57BL6 strains.…”

Section: Animalsmentioning

confidence: 99%

“…MT-III and MT-IV isoforms exist in neural tissue and squamous epithelium, respectively (Masters et al, 1994b;Quaife et al, 1994). Recently, MT-null transgenic mice that are deficient in MT-I and MT-II were produced by the gene-targeting technique (Masters et al, 1994a;Michalska and Choo, 1993). Several studies have shown that MT-null mice have an increased sensitivity to oxidative stress induced by paraquat (Sato et al, 1996), ultraviolet (Hanada et al, 1998), or acetaminophen (Rofe et al, 1998;Zhang et al, 1999;Liu et al, 1999).…”

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confidence: 99%

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Cytoprotection by Metallothionein Against Gastroduodenal Mucosal Injury Caused by Ethanol in Mice

Takano

Satoh

Shimada

et al. 2000

Laboratory Investigation

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SUMMARY:Metallothionein (MT) is a small, cysteine-rich protein that can act as a free radical scavenger at least in vitro. To test the hypothesis that MT participates in gastroduodenal cytoprotection, we studied sensitivity to gastroduodenal mucosal injury caused by ethanol in MT-null mice that have null mutations in MT-I and MT-II genes. MT-null mice and wild-type mice were orally treated with ethanol (60% or 99.5%, 0.2 ml/mouse). The macroscopic gastric lesion indices were significantly higher in MT-null mice than in wild-type mice 90 minutes after ethanol treatment. Histopathological examination in ethanol-treated MT-null mice showed vacuolar degeneration, necrosis of the epithelial cells, and hemorrhage throughout the tunica mucosa. Moreover, the duodenum also showed morphologic changes, including marked degeneration and coagulative necrosis of the entire villi, desquamation of the degenerated epithelial cells, and hemorrhage. In contrast, histopathologic changes were less prominent in the wild-type mice treated with ethanol. MT was not detected either in the stomach or duodenum of MT-null mice, whereas gastric and duodenal zinc contents were not significantly different between MT-null mice and wild-type mice. These results provide direct evidence that intrinsic MT plays a cytoprotective role in gastroduodenal mucosal injury caused by ethanol. (Lab Invest 2000, 80:371-377).

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Section: Animalsmentioning

confidence: 99%

mentioning

confidence: 99%

Cytoprotection by Metallothionein Against Gastroduodenal Mucosal Injury Caused by Ethanol in Mice

Takano

Satoh

Shimada

et al. 2000

Laboratory Investigation

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“…Although transgenic mice lacking functional MT genes have been shown to grow and reproduce normally (Michalska & Choo, 1993;Masters et al, 1994), they, however, display increased sensitivity to chemical stress, compared to wild-type mice (Lazo et al. 1995;Philcox et al, 1995;Rofe et al, 1996).…”

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confidence: 99%

Monitoring metal ion flux in reactions of metallothionein and drug‐modified metallothionein by electrospray mass spectrometry

et al. 1998

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The capabilities of electrospray ionization mass spectrometry are demonstrated for monitoring the flux of metal ions out of and into the metalloprotein rabbit liver metallothionein and, in one example, chlorambucil-alkylated metallothionein. Metal ion transfers may be followed as the reactions proceed in situ to provide kinetic information. More uniquely to this technique, metal ion stoichiometries may be determined for reaction intermediates and products. Partners used in these studies include EDTA, carbonic anhydrase, a zinc-bound hexamer of insulin, and the core domain of bacteriophage T4 gene 32 protein, a binding protein for single-stranded DNA.Keywords: acquired drug resistance; DNA binding protein; electrospray mass spectrometry; insulin; metal ion flux; metallothionein; stress response Metallothioneins (MT) comprise a family of small metal binding proteins that occurs widely throughout the animal kingdom. Plants and bacteria also produce types of metallothioneins. Vertebrate MTs share essentially the same structure (Kagi, 1993), with 20 cysteines coordinating seven divalent metal cations (Schultze et al., 1988; Robbins et al., 1991). TLVO domains are joined by a linker region, the N-terminal or P-domain binding three metal cations and the C-terminal or cy-domain binding four metal cations. Metallothioneins in invertebrate species also contain multiple cysteine side chains that bind metal cations.Although it would seem that a protein as widespread as MT must play a biological role that is essential for the survival of organisms (Vallee, 1995), the function of MT has been a subject for debate since it was discovered 40 years ago (Margoshes & Vallee, 1957). One function often cited for MT is the detoxification of heavy metals, cadmium in particular. However, the incidence of toxic concentrations of heavy metals in the environment is sporadic; thus, the need to detoxify heavy metals does not seem to account for the ability of virtually all living cells to synthesize metallothioneins transcriptionally or enzymatically (Steffens, 1990;

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“…7 Nevertheless, results from 2 independent groups led to the conclusion that unexposed MT-1/2 knockout mice are viable and reproduce normally. 8,9 Although the role of MT in cisplatin susceptibility of normal kidney cells appears to be clear, the situation remains inconclusive for tumor cells. A large number of experiments have shown MT involvement in anti-cancer drug resistance, especially against platinum compounds.…”

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confidence: 99%

Metallothionein expression in ovarian cancer in relation to histopathological parameters and molecular markers of prognosis

Hengstler

Pilch²,

Schmidt³

et al. 2001

Int. J. Cancer

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Targeting and germ-line transmission of a null mutation at the metallothionein I and II loci in mouse.

Cited by 356 publications

References 27 publications

Cytoprotection by Metallothionein Against Gastroduodenal Mucosal Injury Caused by Ethanol in Mice

Cytoprotection by Metallothionein Against Gastroduodenal Mucosal Injury Caused by Ethanol in Mice

Monitoring metal ion flux in reactions of metallothionein and drug‐modified metallothionein by electrospray mass spectrometry

Metallothionein expression in ovarian cancer in relation to histopathological parameters and molecular markers of prognosis

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