RGD Reference Report - Inherited copper toxicity in Long-Evans cinnamon rats exhibiting spontaneous hepatitis: a model of Wilson's disease. - Rat Genome Database

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Inherited copper toxicity in Long-Evans cinnamon rats exhibiting spontaneous hepatitis: a model of Wilson's disease.

Authors: Okayasu, T  Tochimaru, H  Hyuga, T  Takahashi, T  Takekoshi, Y  Li, Y  Togashi, Y  Takeichi, N  Kasai, N  Arashima, S 
Citation: Okayasu T, etal., Pediatr Res. 1992 Mar;31(3):253-7. doi: 10.1203/00006450-199203000-00011.
RGD ID: 25823154
Pubmed: PMID:1561010   (View Abstract at PubMed)
DOI: DOI:10.1203/00006450-199203000-00011   (Journal Full-text)

The copper concentrations in organs of developing Long-Evans Cinnamon (LEC) rats (2 d to 13 mo) were measured to elucidate the pathogenesis of their hereditary hepatitis. Hepatic copper contents of LEC rats were significantly higher than those of control rats (26 to 92 times higher). The subcellular distribution of hepatic copper indicated that the nuclear and large granular fractions had been saturated and the cytosol fraction contained about 70% of all the hepatic copper in LEC rats. The serum concentrations of copper and ceruloplasmin were significantly lower than those of control rats from the 4th wk (10-12% and 5-19%, respectively). Copper contents in kidney of LEC rats did not exhibit an increase over those of control rats until 12 wk, but then increased to nearly 40 times higher during fulminant hepatic failure. Accumulation of copper was not detected in the brain or small intestines of LEC rats until 13 mo. The hepatic copper concentration, its subcellular distribution, and serum copper concentration of F1 rats (LEC x Long-Evans Agouti) exhibited the same levels as those of Long-Evans Agouti rats. In addition to their similarity concerning inheritance of autosomal recessive means and clinical course, we found causality relating copper accumulation to the pathogenesis of the disease. We propose that LEC rats will be the most promising animal model for the study of Wilson's disease.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ATP7BHumanWilson disease  ISOAtp7b (Rattus norvegicus) RGD 
Atp7bRatWilson disease  IAGP  RGD 
Atp7bMouseWilson disease  ISOAtp7b (Rattus norvegicus) RGD 
Atp7bhtsRatWilson disease  IAGP  RGD 
LEC/HokRatWilson disease MODEL: spontaneousIAGP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Atp7bRatdecreased circulating ceruloplasmin level  IAGP compared to LEA/HokRGD 
Atp7bhtsRatdecreased circulating ceruloplasmin level  IAGP compared to LEA/HokRGD 
LEC/HokRatdecreased circulating ceruloplasmin level  IAGP compared to LEA/HokRGD 
Atp7bRatincreased liver copper level  IAGP compared to LEA/HokRGD 
Atp7bhtsRatincreased liver copper level  IAGP compared to LEA/HokRGD 
LEC/HokRatincreased liver copper level  IAGP compared to LEA/HokRGD 

Objects Annotated

Genes (Rattus norvegicus)
Atp7b  (ATPase copper transporting beta)
Atp7bhts  (ATPase copper transporting beta; hepatitis)

Genes (Mus musculus)
Atp7b  (ATPase, Cu++ transporting, beta polypeptide)

Genes (Homo sapiens)
ATP7B  (ATPase copper transporting beta)

Strains
LEC/Hok  (Long Evans Cinnamon)


Additional Information