RGD Reference Report - A target-selected Apc-mutant rat kindred enhances the modeling of familial human colon cancer. - Rat Genome Database

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A target-selected Apc-mutant rat kindred enhances the modeling of familial human colon cancer.

Authors: Amos-Landgraf, JM  Kwong, LN  Kendziorski, CM  Reichelderfer, M  Torrealba, J  Weichert, J  Haag, JD  Chen, KS  Waller, JL  Gould, MN  Dove, WF 
Citation: Amos-Landgraf JM, etal., Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4036-41. Epub 2007 Feb 27.
RGD ID: 1601201
Pubmed: PMID:17360473   (View Abstract at PubMed)
PMCID: PMC1805486   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0611690104   (Journal Full-text)

Progress toward the understanding and management of human colon cancer can be significantly advanced if appropriate experimental platforms become available. We have investigated whether a rat model carrying a knockout allele in the gatekeeper gene Adenomatous polyposis coli (Apc) recapitulates familial colon cancer of the human more closely than existing murine models. We have established a mutagen-induced nonsense allele of the rat Apc gene on an inbred F344/NTac (F344) genetic background. Carriers of this mutant allele develop multiple neoplasms with a distribution between the colon and small intestine that closely simulates that found in human familial adenomatous polyposis patients. To distinguish this phenotype from the predominantly small intestinal phenotype found in most Apc-mutant mouse strains, this strain has been designated the polyposis in the rat colon (Pirc) kindred. The Pirc rat kindred provides several unique and favorable features for the study of colon cancer. Tumor-bearing Pirc rats can live at least 17 months, carrying a significant colonic tumor burden. These tumors can be imaged both by micro computed tomography scanning and by classical endoscopy, enabling longitudinal studies of tumor genotype and phenotype as a function of response to chemopreventive and therapeutic regimes. The metacentric character of the rat karyotype, like that of the human and unlike the acrocentric mouse, has enabled us to demonstrate that the loss of the wild-type Apc allele in tumors does not involve chromosome loss. We believe that the Pirc rat kindred can address many of the current gaps in the modeling of human colon cancer.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
APCHumananemia  ISOApc (Rattus norvegicus) RGD 
ApcRatanemia  IMP  RGD 
ApcMouseanemia  ISOApc (Rattus norvegicus) RGD 
ApcPircRatanemia  IMP  RGD 
F344-ApcPirc/UwmRatanemia  IMP  RGD 
APCHumancolon adenocarcinoma  ISOApc (Rattus norvegicus)associated with Adenomatous Polyposis Coli and DNA:point mutation:CDS:p.K1137X (3409A>T) (rat)RGD 
ApcRatcolon adenocarcinoma  IMP associated with Adenomatous Polyposis Coli and DNA:point mutation:CDS:p.K1137X (3409A>T) (rat)RGD 
ApcMousecolon adenocarcinoma  ISOApc (Rattus norvegicus)associated with Adenomatous Polyposis Coli and DNA:point mutation:CDS:p.K1137X (3409A>T) (rat)RGD 
ApcPircRatcolon adenocarcinoma  IMP associated with Adenomatous Polyposis ColiRGD 
APCHumanColonic Neoplasms  ISOApc (Rattus norvegicus) RGD 
ApcRatColonic Neoplasms  IMP  RGD 
ApcMouseColonic Neoplasms  ISOApc (Rattus norvegicus) RGD 
ApcPircRatColonic Neoplasms  IMP  RGD 
F344-ApcPirc/UwmRatColonic Neoplasms  IMP  RGD 
APCHumanColonic Polyps  ISOApc (Rattus norvegicus) RGD 
ApcRatColonic Polyps  IMP  RGD 
ApcMouseColonic Polyps  ISOApc (Rattus norvegicus) RGD 
ApcPircRatColonic Polyps  IMP  RGD 
F344-ApcPirc/UwmRatColonic Polyps  IMP  RGD 
APCHumanfamilial adenomatous polyposis  ISOApc (Rattus norvegicus)DNA:point mutation:CDS:p.K1137X (3409A>T) (rat)RGD 
ApcRatfamilial adenomatous polyposis  IMP DNA:point mutation:CDS:p.K1137X (3409A>T) (rat)RGD 
ApcMousefamilial adenomatous polyposis  ISOApc (Rattus norvegicus)DNA:point mutation:CDS:p.K1137X (3409A>T) (rat)RGD 
ApcPircRatfamilial adenomatous polyposis  IMP  RGD 
F344-ApcPirc/UwmRatfamilial adenomatous polyposis  IMP  RGD 
APCHumanIntestinal Neoplasms  ISOApc (Rattus norvegicus) RGD 
ApcRatIntestinal Neoplasms  IMP  RGD 
ApcMouseIntestinal Neoplasms  ISOApc (Rattus norvegicus) RGD 
ApcPircRatIntestinal Neoplasms  IMP  RGD 
F344-ApcPirc/UwmRatIntestinal Neoplasms  IMP  RGD 
APCHumanJaw Neoplasms  ISOApc (Rattus norvegicus) RGD 
ApcRatJaw Neoplasms  IMP  RGD 
ApcMouseJaw Neoplasms  ISOApc (Rattus norvegicus) RGD 
ApcPircRatJaw Neoplasms  IMP  RGD 
F344-ApcPirc/UwmRatJaw Neoplasms penetranceIMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ApcRatanemia sexual_dimorphismIMP compared to femalesRGD 
ApcPircRatanemia sexual_dimorphismIMP compared to femalesRGD 
F344-ApcPirc/UwmRatanemia sexual_dimorphismIMP compared to femalesRGD 
ApcRatcolon polyps  IMP  RGD 
ApcPircRatcolon polyps  IMP  RGD 
F344-ApcPirc/UwmRatcolon polyps  IMP  RGD 
ApcRatextended life span sexual_dimorphismIMP compared to malesRGD 
ApcPircRatextended life span sexual_dimorphismIMP compared to malesRGD 
F344-ApcPirc/UwmRatextended life span sexual_dimorphismIMP compared to malesRGD 
ApcRatincreased colon adenoma incidence  IMP compared to treated females and mock treated malesRGD 
ApcPircRatincreased colon adenoma incidence  IMP compared to treated females and mock treated malesRGD 
F344-ApcPirc/UwmRatincreased colon adenoma incidence inducedIMPN-ethyl-N-nitrosoureacompared to treated females and mock treated malesRGD 
ApcRatincreased intestinal adenocarcinoma incidence sexual_dimorphismIMPN-ethyl-N-nitrosoureacompared to treated femalesRGD 
ApcPircRatincreased intestinal adenocarcinoma incidence sexual_dimorphismIMPN-ethyl-N-nitrosoureacompared to treated femalesRGD 
F344-ApcPirc/UwmRatincreased intestinal adenocarcinoma incidence sexual_dimorphismIMPN-ethyl-N-nitrosoureacompared to treated femalesRGD 
ApcRatrectal hemorrhage sexual_dimorphismIMP compared to femalesRGD 
ApcPircRatrectal hemorrhage sexual_dimorphismIMP compared to femalesRGD 
F344-ApcPirc/UwmRatrectal hemorrhage sexual_dimorphismIMP compared to femalesRGD 
ApcRatweight loss sexual_dimorphismIMP compared to femalesRGD 
ApcPircRatweight loss sexual_dimorphismIMP compared to femalesRGD 
F344-ApcPirc/UwmRatweight loss sexual_dimorphismIMP compared to femalesRGD 
Objects Annotated

Genes (Rattus norvegicus)
Apc  (APC regulator of WNT signaling pathway)
ApcPirc  (APC, WNT signaling pathway regulator; polyposis in the rat colon)

Genes (Mus musculus)
Apc  (APC, WNT signaling pathway regulator)

Genes (Homo sapiens)
APC  (APC regulator of WNT signaling pathway)

Strains
F344-ApcPirc/Uwm  (NA)


Additional Information