Merck
  • Restoration of copper metabolism and rescue of hepatic abnormalities in LEC rats, an animal model of Wilson disease, by expression of human ATP7B gene.

Restoration of copper metabolism and rescue of hepatic abnormalities in LEC rats, an animal model of Wilson disease, by expression of human ATP7B gene.

Biochimica et biophysica acta (2004-10-30)
Yan Meng, Ichiro Miyoshi, Masumi Hirabayashi, Mu Su, Yasumasa Mototani, Tadashi Okamura, Kunihiko Terada, Masatsugu Ueda, Katsuhiko Enomoto, Toshihiro Sugiyama, Noriyuki Kasai
ABSTRACT

Hepatic abnormalities in Long-Evans Cinnamon (LEC) rats, an animal model of Wilson disease (WD), were restored by the expression of the human ATP7B cDNA under the control of CAG promoter. Expression of ATP7B transcript and protein in the liver of the transgenic rats resulted in the restoration of biosynthesis of holoceruloplasmin and biliary copper excretion. Meanwhile, transgenic rats showed striking improvements in their hepatic abnormalities, i.e., rescue from fulminant hepatitis, late onset of hepatic cholangiofibrosis, suppression of hepatocellular carcinoma and much improved survival rates. Moreover, dramatic decreases were noted both in the levels of hepatic copper and iron in transgenic rats before the occurrence of hepatitis. These results indicated that the human ATP7B product compensated for the deficiency of the endogenous rattus protein and did function in intrahepatic copper transport by secreting copper into the plasma via incorporation into ceruloplasmin and by the excretion of copper into the bile, and that ATP7B is critical to hepatic dysfunctions in WD. This first successful transgenic rescue has important implications for the gene therapy of WD.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Copper, foil, ≥99.8% (complexometric)
Continuous cast copper (O), BCR®, certified reference material, rod
Sigma-Aldrich
Copper, turnings, purum p.a., ≥99.0%
Sigma-Aldrich
Copper, beads, 2-8 mm, ≥99.99% trace metals basis
Sigma-Aldrich
Copper, powder, <75 μm, 99%
Sigma-Aldrich
Copper, foil, thickness 0.025 mm, 99.98% trace metals basis
Sigma-Aldrich
Copper, beads, 2-8 mm, 99.9995% trace metals basis
Sigma-Aldrich
Copper, nanopowder, 40-60 nm particle size (SAXS), ≥99.5% trace metals basis
Sigma-Aldrich
Copper, nanopowder, 60-80 nm particle size (SAXS), ≥99.5% trace metals basis
Copper, IRMM®, certified reference material, 0.1 mm foil
Copper, IRMM®, certified reference material, 0.5 mm wire
Sigma-Aldrich
Copper, shot, −3-+14 mesh, 99%
Sigma-Aldrich
Copper, powder, 99.999% trace metals basis
Sigma-Aldrich
Copper, ACS reagent, granular, 10-40 mesh, ≥99.90%
Sigma-Aldrich
Copper, powder (spheroidal), 10-25 μm, 98%
Sigma-Aldrich
Copper, powder (dendritic), <45 μm, 99.7% trace metals basis
Copper (O), BCR®, certified reference material, rod
Sigma-Aldrich
Copper, powder, <425 μm, 99.5% trace metals basis