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
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
anemia  ISOApc (Rattus norvegicus)1601201; 1601201 RGD 
anemia  IMP 1601201; 1601201; 1601201 RGD 
colon adenocarcinoma  ISOApc (Rattus norvegicus)1601201; 1601201associated with Adenomatous Polyposis Coli and DNA:point mutation:CDS:p.K1137X (3409A>T) (rat)RGD 
colon adenocarcinoma  IMP 1601201associated with Adenomatous Polyposis Coli and DNA:point mutation:CDS:p.K1137X (3409A>T) (rat)RGD 
colon adenocarcinoma  IMP 1601201associated with Adenomatous Polyposis ColiRGD 
Colonic Neoplasms  ISOApc (Rattus norvegicus)1601201; 1601201 RGD 
Colonic Neoplasms  IMP 1601201; 1601201; 1601201 RGD 
Colonic Polyps  ISOApc (Rattus norvegicus)1601201; 1601201 RGD 
Colonic Polyps  IMP 1601201; 1601201; 1601201 RGD 
familial adenomatous polyposis  ISOApc (Rattus norvegicus)1601201; 1601201DNA:point mutation:CDS:p.K1137X (3409A>T) (rat)RGD 
familial adenomatous polyposis  IMP 1601201DNA:point mutation:CDS:p.K1137X (3409A>T) (rat)RGD 
familial adenomatous polyposis  IMP 1601201; 1601201 RGD 
Intestinal Neoplasms  ISOApc (Rattus norvegicus)1601201; 1601201 RGD 
Intestinal Neoplasms  IMP 1601201; 1601201; 1601201 RGD 
Jaw Neoplasms  ISOApc (Rattus norvegicus)1601201; 1601201 RGD 
Jaw Neoplasms  IMP 1601201; 1601201 RGD 
Jaw Neoplasms penetranceIMP 1601201 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
anemia sexual_dimorphismIMP 1601201; 1601201; 1601201compared to femalesRGD 
colon polyps  IMP 1601201; 1601201; 1601201 RGD 
extended life span sexual_dimorphismIMP 1601201; 1601201; 1601201compared to malesRGD 
increased colon adenoma incidence  IMP 1601201; 1601201compared to treated females and mock treated malesRGD 
increased colon adenoma incidence inducedIMPN-ethyl-N-nitrosourea1601201compared to treated females and mock treated malesRGD 
increased intestinal adenocarcinoma incidence sexual_dimorphismIMPN-ethyl-N-nitrosourea1601201; 1601201; 1601201compared to treated femalesRGD 
rectal hemorrhage sexual_dimorphismIMP 1601201; 1601201; 1601201compared to femalesRGD 
weight loss sexual_dimorphismIMP 1601201; 1601201; 1601201compared 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