WILSONS-DISEASE GENE IS HOMOLOGOUS TO HTS CAUSING ABNORMAL COPPER TRANSPORT IN LONG-EVANS CINNAMON RATS

Background/Aims: The Long-Evans Cinnamon (LEC) mutant rat shows an excess copper accumulation in the liver and low serum ceruloplasmin activity. The disorder is controlled by a single autosomal recessive gene designated as hts. Wilson's disease is an autosomal recessive disorder of copper metabolism characterized by abnormal copper accumulation in the liver and tow serum ceruloplasmin activity. The gene responsible for Wilson's disease has recently been isolated. The present study was designed to examine whether the LEC rat is an ideal animal model for Wilson's disease from a genetic point of view. Methods: For chromosomal mapping of hts, genetic linkage analysis using rat microsatellite marker loci was performed. Furthermore, cosegregation between hts and a rat counterpart of the Wilson's disease gene was analyzed. Results: hts was finely mapped to rat chromosome 16. Complete cosegregation between hts and a rat counterpart of the Wilson's disease gene was detected. Conclusions: hts is likely to correspond to a rat homologue of the Wilson's disease gene. The present results allow us to propose that the LEC rat is an ideal animal model for Wilson's disease.