The ubiquitously expressed MURR1 protein is absent in canine copper toxicosis

J Hepatol. 2003 Nov;39(5):703-9. doi: 10.1016/s0168-8278(03)00380-5.


Background/aims: Copper toxicosis (CT) in Bedlington terriers is an autosomal recessive disorder characterized by massive lysosomal copper accumulation in livers of affected dogs, and a defect in the biliary excretion of this metal. We propose that MURR1, the gene defective in canine CT, has a role in the regulation of copper excretion into bile during copper overload.

Methods: Polyclonal antibodies raised against full-length recombinant human MURR1 were used for immunoblot analysis and indirect immunofluorescence studies.

Results: Using Western blot analysis, these antibodies abundantly detected MURR1 as a 23 kDa protein in liver extracts of mice and dogs, but MURR1 was undetectable in the livers of affected Bedlington terriers. MURR1 was also detected in different tissues and cell lines; in cell lines the protein was found both in cytosol and membrane preparations. Consistent with this observation, indirect immunofluorescence staining revealed that in some cells MURR1 was associated with a vesicular compartment diffusely localized throughout the cell.

Conclusions: The genomic deletion in MURR1 results in complete absence of MURR1 protein. Based on the unanticipated subcellular localization, our results suggest a role for MURR1 in the regulation of vesicular copper sequestration during copper overload.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Carrier Proteins
  • Cell Line
  • Copper / metabolism*
  • Dog Diseases / genetics*
  • Dog Diseases / metabolism
  • Dogs
  • Female
  • Gene Deletion*
  • Genetic Diseases, Inborn / veterinary*
  • Humans
  • Immune Sera
  • Liver / metabolism*
  • Mice
  • Proteins / genetics
  • Proteins / metabolism*
  • Subcellular Fractions / metabolism


  • Adaptor Proteins, Signal Transducing
  • COMMD1 protein, human
  • Carrier Proteins
  • Immune Sera
  • Proteins
  • Copper