Abnormal Copper-Thionein Synthesis and Impaired Copper Utilization in Mutated Brindled Mice: Model for Menkes' Disease

Prins, Hans W.; Hamer, C.J.A. van den

doi:10.1093/jn/110.1.151

Cited by 40 publications

(11 citation statements)

References 19 publications

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“…However, the same explanation cannot be applied to the elevated Mt-i mRNA levels in kidney and intestine of newborn deletion homozygotes, since in these tissues the Mt-i gene is normally under positive regulation by glucocorticoids. Curiously, tissuespecific effects on metallothionein mRNA expression analogous to those reported here are also caused by another genetic system in the mouse, the recessive X chromosomelinked mottled mutations (6,26,27), emphasizing the significance of the genetic and developmental control of heavymetal homeostasis and metabolism.…”

Section: Discussionsupporting

confidence: 63%

Metallothionein mRNA expression in mice homozygous for chromosomal deletions around the albino locus.

DeFranco¹,

Morris²,

Leonard³

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

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Deletions in chromosome 7 of the mouse affect the expression of the metallothionein gene Mt-1, which maps on chromosome 8, and steady-state levels of Mt-1 mRNA are reduced to 15-40% of normal in livers of newborn mice homozygous for either the c3H or c14CoS deletion. Glucocorticoids fail to induce hepatic Mt-1 mRNA levels in deletion homozygotes in contrast to normal littermates. However, zinc chloride is effective in inducing Mt-1 mRNA levels in livers of deletion homozygotes as well as of their normal littermates. Other tissues (e.g., kidney and intestine) of deletion homozygotes express basal levels of Mt-1 mRNA higher than those of normal littermates. In the intestine these are furthermore inducible by both hormonal and metal agents. Thus, loss of inducibility of the Mt-1 gene in deletion homozygotes concerns glucocorticoids only and is furthermore restricted to specific cell types (i.e., hepatocytes). The trans-acting factor(s) normally encoded in the deleted region of chromosome 7 appears to be instrumental in conferring on the metallothionein gene in hepatocytes the essential competence to respond to hormonal inducing signals.

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Section: Discussionsupporting

confidence: 63%

Metallothionein mRNA expression in mice homozygous for chromosomal deletions around the albino locus.

DeFranco¹,

Morris²,

Leonard³

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

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“…These can be divided into two categories. One is that the basic defect is an abnormal transport of cop per [Prins and Van den Hamer, 1980;Bone witz and Howell, 1981;Packman and O'Toole, 1984;Leone et al, 1985;Sone et al, 1987;Packman et al, 1987], whereas the other is that the basic defect is an abnormal regulation of MT genes, causing a greater accumulation of intracellular copper [Prins and Van den Hamer, 1980;Riordan and Jo licoeur-Paquet, 1982;Schmidt et al, 1984;Leone et al, 1985], Our findings have indi cated that there is a greater amount of MT in macular kidney compared to normal kidney [unpubl. data].…”

Section: Discussionmentioning

confidence: 70%

Copper Metabolism in the Macular Mutant Mouse: An Animal Model of Menkes’s Kinky-Hair Disease

1988

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The tissue copper contents were measured in mutant (hemizygous macular male and homozygous macular female), heterozygous macular female and normal mice. The copper content in kidney and small intestine from 7-day-old mutant and heterozygote were extremely high compared to normal mice, whereas the copper content in other tissues (liver, brain, spleen and serum) was low. Copper content in whole body of mutant mice was extremely low at three stages (18 days gestation, 1 day old, and 7 days old) compared to normal mice with the exception of the mutant fetus at 14 days of gestation. Renal copper contents in the mutant fetus at 18 days of gestation and in the 1-day-old mutant were not changed compared to normal mice, whereas that in 7- and 14-day-old mutant mice was significantly elevated. Hepatic copper content of the mutant mice was extremely low at all stages compared to normal mice. Copper therapy was applied to 7-day-old mutant mice. At 1 day after injection, hepatic copper content in the mutants had increased slightly in comparison with the normal control mice, whereas renal copper content was extremely increased. At 7 days after injection, hepatic copper content in the mutants was decreased greatly in comparison with normal control mice, whereas an increase in renal copper content had remained.

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“…The control of MT gene expression by glucocorticoid hormones (3,4) is probably involved in the regulation of plasma Zn2+ concentration (5). Defects in MT gene expression have been suggested to be the cause for several disorders of trace metal metabolism in man-i.e., Menkes kinky hair syndrome (6,7), Wilson disease (8), and acrodermatitis enteropathica (9). Yet, no direct involvement of the MT genes in any one of these diseases has been demonstrated.…”

mentioning

confidence: 99%

Human metallothionein genes are clustered on chromosome 16.

Karin¹,

Eddy²,

Henry³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

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Abnormal Copper-Thionein Synthesis and Impaired Copper Utilization in Mutated Brindled Mice: Model for Menkes' Disease

Cited by 40 publications

References 19 publications

Metallothionein mRNA expression in mice homozygous for chromosomal deletions around the albino locus.

Metallothionein mRNA expression in mice homozygous for chromosomal deletions around the albino locus.

Copper Metabolism in the Macular Mutant Mouse: An Animal Model of Menkes’s Kinky-Hair Disease

Human metallothionein genes are clustered on chromosome 16.

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