Prenatal Treatment of Mosaic Mice (Atp7a mo-ms) Mouse Model for Menkes Disease, with Copper Combined by Dimethyldithiocarbamate (DMDTC)

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Prenatal Treatment of Mosaic Mice (Atp7a mo-ms) Mouse Model for Menkes Disease, with Copper Combined by Dimethyldithiocarbamate (DMDTC)

Menkes disease is a fatal neurodegenerative disorder in infants caused by mutations in the gene ATP7A which encodes a copper (Cu) transporter. Defects in ATP7A lead to accumulated copper in the small intestine and kidneys and to copper deficiencies in the brain and the liver. The copper level in the kidney in postnatal copper-treated Menkes patients may reach toxic levels. The mouse model, mosa...

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Mutation in the CPC motif-containing 6th transmembrane domain affects intracellular localization, trafficking and copper transport efficiency of ATP7A protein in mosaic mutant mice--an animal model of Menkes disease.

Copper is an essential micronutrient for all living organisms. ATP7A protein is a copper-transporting ATPase which plays a vital role in the maintenance of cellular copper homeostasis in mammals. This protein is retained within the trans-Golgi network, but after binding copper it can be translocated to the cell membrane to participate in the efflux of excess Cu. Mutation of the ATP7A gene in hu...

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Alteration of copper physiology in mice overexpressing the human Menkes protein ATP7A.

The Menkes protein (ATP7A) is defective in the Cu deficiency disorder Menkes disease and is an important contributor to the maintenance of physiological Cu homeostasis. To investigate more fully the role of ATP7A, transgenic mice expressing the human Menkes gene ATP7A from chicken beta-actin composite promoter (CAG) were produced. The transgenic mice expressed ATP7A in lung, heart, liver, kidne...

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Molecular basis of the brindled mouse mutant (Mo(br)): a murine model of Menkes disease.

The brindled mouse mutant (Mo(br)) is the closest animal model of the human genetic copper deficiency, Menkes disease, which is presumed to be due to a mutation at the X-linked mottled locus (Mo). The mutant mice are hypopigmented and die at around 15 days after birth, but can be saved by treatment with copper before the 10th postnatal day. Menkes disease has been shown to be due to mutations o...

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A copper treatable Menkes disease mutation associated with defective trafficking of a functional Menkes copper ATPase.

Copper dependency in humans is most dramatically illustrated in Menkes disease, an X linked recessive copper deficiency disorder that is generally lethal in early childhood. 2 Menkes disease is caused by mutations in a transmembrane copper transporting P type ATPase, MNK (or ATP7A), which is expressed in virtually all non-hepatic tissues. Studies using cultured cells suggest that MNK is located...

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ژورنال

عنوان ژورنال: PLoS ONE

سال: 2012

ISSN: 1932-6203

DOI: 10.1371/journal.pone.0040400