Excellent model for study of human familial colon cancer
ENU-induced point mutation results in a truncating mutation in the Apc gene at a site corresponding to the human mutation hotspot region of the gene
Heterozygotes develop multiple tumors in the small intestine and colon by 2-4 months of age
Pirc tumors closely resemble those in humans in terms of histopathology and morphology as well as distribution between intestine and colon
Longer lifespan compared to related mouse models (10-15 months)
Tumors may be visualized by CT, endoscopy or dissection
Origin: The Pirc rat was developed by William F. Dove and James Amos-Landgraf, et al. at the University of Wisconsin School of Medicine and Public Health. The model was created through N-ethyl-N-nitrosourea (ENU) treatment of F344/NTac males and screening of their progeny to identify the Pirc founder, which harbored a point mutation at Apc nucleotide 3409. This point mutation created a stop codon at codon 1137 of the gene. The founder was backcrossed at least 7 generations to the wild type F344/NTac strain to eliminate other possible ENU-induced mutations. Taconic received stock in July 2008 from the Dove laboratory. The line was embryo transfer derived, and the colony was maintained through breeding of heterozygotes to wild types.
Amos-Landgraf JM, Kwong LN, Kendziorski CM, Reichelderfer M, Torrealba J, Weichert J, Haag JD, Chen K-S, Waller JL, Gould MN, Dove WF. (2007) A target-selected Apc-mutant rat kindred enhances the modeling of familial colon cancer. Proc Natl Acad Sci USA 104(10):4036-4041
Amos-Landgraf JM, Irving AA, Hartman C, Hunter A, Laube B, Chen X, Clipson L, Newton MA, Dove WF. (2012) Monoallelic silencing and haploinsufficiency in early murine intestinal neoplasms. Proc Natl Acad Sci U S A. 109(6):2060-5
Femia AP, Luceri C, Soares PV, Lodovici M, Caderni G. (2014) Multiple mucin depleted foci, high proliferation and low apoptotic response in the onset of colon carcinogenesis of the PIRC rat, mutated in Apc. Int J Cancer. 2014 Sep 25.
[Epub ahead of print]