RGD Reference Report - Role of Atp7b gene in spontaneous and N-diethylnitrosamine-induced carcinogenesis in a new congenic strain, WKAH.C-Atp7b rats. - Rat Genome Database

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Role of Atp7b gene in spontaneous and N-diethylnitrosamine-induced carcinogenesis in a new congenic strain, WKAH.C-Atp7b rats.

Authors: Minami, T  Kaneda, S  Otsuka, T  Jiao, Z  Suzuki, Y  Yamada, T  Matsumoto, K  Izumi, K 
Citation: Minami T, etal., Jpn J Cancer Res 2001 Aug;92(8):841-7.
RGD ID: 1302456
Pubmed: PMID:11509115   (View Abstract at PubMed)
PMCID: PMC5903424   (View Article at PubMed Central)

To examine whether Long-Evans Cinnamon (LEC) rats, a mutant rat model of Wilson's disease, have a susceptibility gene(s) to hepatocarcinogenesis in addition to the causative gene, Atp7b, we established a new congenic strain, WKAH.C-Atp7b rats, in which the Atp7b gene of the LEC rats is inserted into the normal Wistar-King Aptekman Hokkaido (WKAH) background. Hepatocellular tumors developed spontaneously in both sexes of WKAH.C-Atp7b rats, their incidence being slightly lower than that in LEC rats. Incidences of spontaneous liver tumors in LEC, WKAH.C-Atp7b and WKAH rats correlated with hepatic copper and iron concentrations. Medium-term liver bioassay showed that LEC rats were more susceptible to the induction of glutathione S-transferase placental form-positive preneoplastic foci than WKAH.C-Atp7b rats, and WKAH.C-Atp7b rats were more susceptible than WKAH rats. In an N-diethylnitrosamine (DEN)-induced long-term carcinogenicity study, 1) LEC rats were similarly or rather less susceptible to hepatocellular tumors than WKAH.C-Atp7b and WKAH rats, indicating that the progression of the preneoplastic foci to liver cancer in LEC rats was worse than that in WKAH.C-Atp7b and WKAH rats, 2) the incidences of kidney tumors in LEC and WKAH.C-Atp7b rats were higher than that in WKAH rats and high copper concentrations in the kidneys were observed in LEC and WKAH.C-Atp7b rats, 3) LEC rats were resistant to lung carcinogenesis. These data indicate that the susceptibility of LEC rats to liver and kidney carcinogenesis could be explained by Atp7b gene mutation and that the susceptibility to lung carcinogenesis is controlled by gene(s) other than Atp7b.

RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ATP7BHumanliver carcinoma  ISOAtp7b (Rattus norvegicus) RGD 
Atp7bRatliver carcinoma  IAGP  RGD 
Atp7bMouseliver carcinoma  ISOAtp7b (Rattus norvegicus) RGD 
Atp7bhtsRatliver carcinoma  IAGP  RGD 
LEC/TjRatliver carcinoma inducedIAGPN-nitrosodiethylamine RGD 
WKAH.LEC-Atp7bhts/TjRatliver carcinoma inducedIAGPN-nitrosodiethylamine RGD 
WKAH/TjRatliver carcinoma inducedIAGPN-nitrosodiethylamine RGD 
ATP7BHumanLiver Neoplasms  ISOAtp7b (Rattus norvegicus) RGD 
ATP7BHumanLiver Neoplasms onsetISOAtp7b (Rattus norvegicus)compared to LEC/TjRGD 
Atp7bRatLiver Neoplasms onsetIAGP compared to LEC/TjRGD 
Atp7bRatLiver Neoplasms  IAGP  RGD 
Atp7bMouseLiver Neoplasms onsetISOAtp7b (Rattus norvegicus)compared to LEC/TjRGD 
Atp7bMouseLiver Neoplasms  ISOAtp7b (Rattus norvegicus) RGD 
Atp7bhtsRatLiver Neoplasms  IAGP  RGD 
Atp7bhtsRatLiver Neoplasms onsetIAGP compared to LEC/TjRGD 
LEC/TjRatLiver Neoplasms  IAGP  RGD 
WKAH.LEC-Atp7bhts/TjRatLiver Neoplasms onsetIAGP compared to LEC/TjRGD 
ATP7BHumanrenal adenoma  ISOAtp7b (Rattus norvegicus) RGD 
Atp7bRatrenal adenoma  IAGP  RGD 
Atp7bMouserenal adenoma  ISOAtp7b (Rattus norvegicus) RGD 
Atp7bhtsRatrenal adenoma  IAGP  RGD 
LEC/TjRatrenal adenoma inducedIAGPN-nitrosodiethylamine RGD 
WKAH.LEC-Atp7bhts/TjRatrenal adenoma inducedIAGPN-nitrosodiethylamine RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Atp7bRatabnormal renal tubule morphology  IAGP  RGD 
Atp7bhtsRatabnormal renal tubule morphology  IAGP  RGD 
WKAH.LEC-Atp7bhts/TjRatabnormal renal tubule morphology  IAGP  RGD 
Atp7bRatdecreased liver iron level  IAGP compared to LEC/TjRGD 
Atp7bhtsRatdecreased liver iron level  IAGP compared to LEC/TjRGD 
WKAH.LEC-Atp7bhts/TjRatdecreased liver iron level  IAGP compared to LEC/TjRGD 
Atp7bRathepatic megalocytosis  IAGP  RGD 
Atp7bhtsRathepatic megalocytosis  IAGP  RGD 
LEC/TjRathepatic megalocytosis  IAGP  RGD 
WKAH.LEC-Atp7bhts/TjRathepatic megalocytosis  IAGP  RGD 
Atp7bRatjaundice  IAGP  RGD 
Atp7bhtsRatjaundice  IAGP  RGD 
LEC/TjRatjaundice  IAGP  RGD 
WKAH.LEC-Atp7bhts/TjRatjaundice  IAGP  RGD 
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)

LEC/Tj  (NA)
WKAH.LEC-Atp7bhts/Tj  (NA)
WKAH/Tj  (Wistar-King A, WKA)

Additional Information