Gene expression in the liver of Long-Evans cinnamon rats during the development of hepatitis.

The Long-Evans cinnamon (LEC) rat, an authentic model for Wilson disease, is characterized by a mutation in the Atp7b gene leading to a defective copper excretion and, as a consequence, to an accumulation of the metal in the liver and copper-associated hepatotoxicity. In the present communication expression profiles of genes in the liver from wild-type Long-Evans agouti (LEA) and LEC rats at different stages of copper accumulation and liver disease were investigated. Disease states were defined according to serum aspartate aminotransferase activity and bilirubin levels in serum and from histopathology of the liver. Gene expression was determined with the Affymetrix RTU34 oligonucleotide array covering 1031 genes. Compared to the LEA rat, the nondiseased LEC rat with already increased hepatic copper level showed an enhanced expression of genes, particularly related to oxidative stress and DNA damage. During the progression of the liver disease, in particular genes related to oxidative stress, DNA damage, apoptosis and inflammation with acute-phase reaction were upregulated.