Toxic milk mice models of Wilson’s disease

Abstract

AbstractWilson’s disease (WD) is a rare genetic disorder inherited as an autosomal recessive trait. The signs and symptoms of this disease are related to dysfunctional ATP7B protein which leads to copper accumulation and cellular damage. The organs that are most commonly affected by WD are the liver and brain. The dysfunctional ATP7B homolog has previously been identified in many different species, including two naturally occurring murine models called toxic milk mice. The aim of this paper was to compare the toxic milk mouse described by Rauch (tx) to that from Jackson Laboratory (txJ) through a review of studies on these two groups of mice. The two mice strains differ in the type of carried mutation and the phenotype of the disease. The data of the studies showed that the tx mice developed mild chronic hepatitis but suffered severe organ destruction with faster progression to full-liver cirrhosis. No changes were noted in the neurological and behavioral status of this strain despite the described toxic accumulation of copper and neuronal destruction in their brain. On the other hand, though the Jackson toxic milk mice (txJ) also presented chronic hepatitis, the condition was a bit milder with slower progression to end-stage disease. Moreover, hepatocyte suitable to perform neurobehavioral research as their phenotype characterized by tremors and locomotor disabilities better corresponds with the cliniconeurological picture of the humans.