A murine model of Menkes disease reveals a physiological function of metallothionein.

Abstract:

:Human Menkes disease and the murine Mottled phenotype are X-linked diseases that result from copper deficiency due to mutations in a copper-effluxing ATPase, designated ATP7A. Male mice with the Mottled-Brindled allele (Mo-brJ) accumulate copper in the intestine, fail to export copper to peripheral organs and die a few weeks after birth. Much of the intestinal copper is bound by metallothionein (MT). To determine the function of MT in the presence of Atp7a deficiency, we crossed Mo-brJ females with males that bear a targeted disruption of the Mt1 and Mt2 genes (Mt-/-). On an Mt -/- background, most Mo-brJ males as well as heterozygous Mo-brJ females die before embryonic day 11. The lethality in Mo-brJ females can be explained by preferential inactivation of the paternal X chromosome in extraembryonic tissues and resultant copper toxicity in the absence of MT. In support of this hypothesis, cell lines derived from Mt -/-, Mo-brJ embryos are very sensitive to copper toxicity.

journal_name

Nat Genet

journal_title

Nature genetics

authors

Kelly EJ,Palmiter RD

doi

10.1038/ng0696-219

subject

Has Abstract

pub_date

1996-06-01 00:00:00

pages

219-22

issue

2

eissn

1061-4036

issn

1546-1718

journal_volume

13

pub_type

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