Table 1 Short characteristics of mice models of Wilson’s disease

From: Toxic milk mice models of Wilson’s disease

  Toxic milk mouse Jackson toxic milk mouse ATP7B−/− mouse
Origin Natural inbred mutation Natural inbred mutation Genetically engineered
Mutation Point mutation 1356 Met—> Val Point mutation 712 Gly—> Asp introduction of an early termination codon in exon 2 of mouse ATP7B mRNA
Natural disease course Progression to full-liver cirrhosis until 1 year Slightly slower progression to liver steatosis and cirrhosis Earlier development of severe liver pathology than in natural inbred models
Earliest notable changes in the liver Nodular fibrosis, bile duct hyperplasia, and inflammatory infiltration at 6 months Increased inflammatory infiltration at 5 months
Mild fibrosis at 6–7 months
Ultrastructural changes,
steatosis, and mild inflammation at 6 weeks
Hepatitis, dysplasia,
and necroinflammation at 4–5 months
Liver morphology in end-stage disease Hepatocyte steatosis, fibrosis, and progression to full-liver cirrhosis Fibrosis with nodular regenerative remodeling, cirrhosis, and rarely HCC Bile duct proliferation, fibrosis, neoplastic proliferation. Regeneration processes often seen in large parts of the liver
Behavioral, neurological, and locomotor changes No evidence of neurological or behavioral disturbances reported Light changes: forelimb usage preference and slower locomotor learning (rotarod) No remarkable neurologic/behavioral symptoms or evident brain pathology were observed
Elevated copper concentration in the liver  +   +   + 
Elevated copper concentration in the brain  +   +   + 
Copper-deficient milk  +   +   + 
Need of cross-fostering  +   + 
Decreased ceruloplasmin concentration  +   +   + 
  1. Met methionine, Val valine, Asp aspartic acid, Gly glycine, HCC hepatocellular carcinoma