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• W2055314963 abstract "The toxic milk (tx) mouse is a non-fatal animal model for the metabolic liver disorder, Wilson's disease. The tx mouse has a mutated gene for a copper-transporting protein, causing early copper accumulation in the liver and late accumulation in other tissues. The present study investigated the efficacy of liver cell transplantation (LCT) to correct the tx mouse phenotype.Congenic hepatocytes were isolated and intrasplenically transplanted into 3-4-month-old tx mice, which were then placed on various copper-loaded diets to examine its influence on repopulation by transplanted cells. The control animals were age-matched untransplanted tx mice. Liver repopulation was determined by comparisons of restriction fragment length polymorphism ratios (DNA and mRNA), and copper levels were measured by atomic absorption spectroscopy.Repopulation in recipient tx mice was detected in 11 of 25 animals (44%) at 4 months after LCT. Dietary copper loading (whether given before or after LCT, or both) provided no growth advantage for donor cells, with similar repopulation incidences in all copper treatment groups. Overall, liver copper levels were significantly lower in repopulated animals (538 +/- 68 microg/g, n = 11) compared to non-repopulated animals (866 +/- 62 microg/g, n = 14) and untreated controls (910 +/- 103 microg/g, n = 6; P < 0.05). This effect was also seen in the kidney and spleen. Brain copper levels remained unchanged.Transplanted liver cells can proliferate and correct a non-fatal metabolic liver disease, with some restoration of hepatic copper homeostasis after 4 months leading to reduced copper levels in the liver and extrahepatic tissues, but not in the brain." @default.
• W2055314963 created "2016-06-24" @default.
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• W2055314963 date "2004-11-01" @default.
• W2055314963 modified "2023-09-26" @default.
• W2055314963 title "Liver cell transplantation leads to repopulation and functional correction in a mouse model of Wilson's disease" @default.
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• W2055314963 doi "https://doi.org/10.1111/j.1440-1746.2004.03451.x" @default.
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