The pleiotropic phenotype of Apc mutations in the mouse: allele specificity and effects of the genetic background.

Genetics
Richard B HalbergWilliam F Dove

Abstract

Familial adenomatous polyposis (FAP) is a human cancer syndrome characterized by the development of hundreds to thousands of colonic polyps and extracolonic lesions including desmoid fibromas, osteomas, epidermoid cysts, and congenital hypertrophy of the pigmented retinal epithelium. Afflicted individuals are heterozygous for mutations in the APC gene. Detailed investigations of mice heterozygous for mutations in the ortholog Apc have shown that other genetic factors strongly influence the phenotype. Here we report qualitative and quantitative modifications of the phenotype of Apc mutants as a function of three genetic variables: Apc allele, p53 allele, and genetic background. We have found major differences between the Apc alleles Min and 1638N in multiplicity and regionality of intestinal tumors, as well as in incidence of extracolonic lesions. By contrast, Min mice homozygous for either of two different knockout alleles of p53 show similar phenotypic effects. These studies illustrate the classic principle that functional genetics is enriched by assessing penetrance and expressivity with allelic series. The mouse permits study of an allelic gene series on multiple genetic backgrounds, thereby leading to a better understanding...Continue Reading

References

Aug 9, 1991·Science·K W KinzlerD McKechnie
Aug 13, 1987·Nature·E SolomonS H Rider
Oct 1, 1969·Annals of Internal Medicine·F P Li, J F Fraumeni
Aug 1, 1995·Developmental Dynamics : an Official Publication of the American Association of Anatomists·A R MoserR L Gardner
Jan 1, 1994·Current Biology : CB·T JacksR A Weinberg
Mar 1, 1994·Gut·A K GurbuzS R Hamilton
Aug 15, 1996·Genes & Development·M NachtT Jacks
Feb 15, 1997·The Journal of Experimental Zoology·K YangM Lipkin
Jun 25, 1998·Molecular and Cellular Biology·Y XuD Baltimore
Sep 2, 1998·Proceedings of the National Academy of Sciences of the United States of America·A R ShoemakerW F Dove
Mar 15, 2000·Proceedings of the National Academy of Sciences of the United States of America·R B HalbergW F Dove
Mar 29, 2000·Proceedings of the National Academy of Sciences of the United States of America·A J RowanI P Tomlinson
Mar 10, 2001·International Journal of Cancer. Journal International Du Cancer·L BertarioUNKNOWN Hereditary Colorectal Tumours Registry
Feb 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·O M SieberK Heinimann
Feb 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Annemieke de VriesTyler Jacks
Mar 21, 2002·Nature Reviews. Cancer·T Soussi, C Béroud
Jun 13, 2002·Proceedings of the National Academy of Sciences of the United States of America·Kevin M HaigisWilliam F Dove
May 2, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·L BertarioUNKNOWN Hereditary Colorectal Tumor Registry
May 14, 2003·Journal of Cancer Research and Clinical Oncology·Hiroki SakaiMasae Tatematsu
Jun 18, 2003·Proceedings of the National Academy of Sciences of the United States of America·Maria Elena MartinezEugene W Gerner
Feb 7, 2004·Science·Lee Hartwell
Jun 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Kevin M HaigisWilliam F Dove
Aug 24, 2004·Oncogene·Rebecca NagyCharis Eng
Jan 8, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Judy E Garber, Kenneth Offit
Mar 3, 2005·BMC Cancer·Roland S CronerKlaus Guenther
Apr 6, 2005·World Journal of Gastroenterology : WJG·Ming DongYu-Ting Dong

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Citations

Jun 19, 2013·Proceedings of the National Academy of Sciences of the United States of America·Kunishige OnumaYoshitaka Hippo
Nov 1, 2011·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Sinan ErtenMehmet Koyutürk
Nov 16, 2010·Carcinogenesis·Darryl Shibata
Dec 15, 2010·BMC Bioinformatics·Gurkan BebekMark R Chance
Sep 9, 2010·PloS One·Vishal N PatelMark R Chance
Aug 14, 2012·International Journal of Vascular Medicine·Kousei OhshimaMasatsugu Horiuchi
Mar 13, 2016·Seminars in Oncology·Farzana L WalcottKathleen A Calzone
Aug 21, 2010·International Journal of Cancer. Journal International Du Cancer·Eric C CheonPaul J Grippo
Apr 25, 2019·International Journal of Cancer. Journal International Du Cancer·Naghma KhanRichard B Halberg
Dec 5, 2019·Pleura and Peritoneum·Timothy ChittleboroughRobert George Ramsay

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