Genetically Modified Mouse Models in Cancer Studies

Overview

Journal Clin Transl Oncol

Specialty Oncology

Date 2008 Dec 11

PMID 19068450

Authors

Javier Santos

Pablo Fernandez-Navarro

Maria Villa-Morales

Laura Gonzalez-Sanchez

Jose Fernandez-Piqueras

Affiliations

Soon will be listed here.

Abstract

Genetically modified animals represent a resource of immense potential for cancer research. Classically, genetic modifications in mice were obtained through selected breeding experiments or treatments with powerful carcinogens capable of inducing random mutagenesis. A new era began in the early 1980s when genetic modifications by inserting foreign DNA genes into the cells of an animal allowed for the development of transgenic mice. Since that moment, genetic modifications have been able to be made in a predetermined way. Gene targeting emerged later as a method of in vivo mutagenesis whereby the sequence of a predetermined gene is selectively modified within an intact cell. In this review we focus on how genetically modified mice can be created to study tumour development, and how these models have contributed to an understanding of the genetic alterations involved in human cancer. We also discuss the strengths and weaknesses of the different mouse models for identifying cancer genes, and understanding the consequences of their alterations in order to obtain the maximum benefit for cancer patients.

References

Marcus D, Rustgi A, Defoe D, Brooks S, McCormick R, Thompson T . Retinal pigment epithelium abnormalities in mice with adenomatous polyposis coli gene disruption. Arch Ophthalmol. 1997; 115(5):645-50. DOI: 10.1001/archopht.1997.01100150647013. View

Garcia-Cao I, Garcia-Cao M, Martin-Caballero J, Criado L, Klatt P, Flores J . "Super p53" mice exhibit enhanced DNA damage response, are tumor resistant and age normally. EMBO J. 2002; 21(22):6225-35. PMC: 137187. DOI: 10.1093/emboj/cdf595. View

Mao J, Balmain A . Genomic approaches to identification of tumour-susceptibility genes using mouse models. Curr Opin Genet Dev. 2003; 13(1):14-9. DOI: 10.1016/s0959-437x(03)00005-4. View

Fodde R, Edelmann W, Yang K, van Leeuwen C, Carlson C, Renault B . A targeted chain-termination mutation in the mouse Apc gene results in multiple intestinal tumors. Proc Natl Acad Sci U S A. 1994; 91(19):8969-73. PMC: 44728. DOI: 10.1073/pnas.91.19.8969. View

Kilby N, Snaith M, Murray J . Site-specific recombinases: tools for genome engineering. Trends Genet. 1993; 9(12):413-21. DOI: 10.1016/0168-9525(93)90104-p. View

Matheu A, Maraver A, Klatt P, Flores I, Garcia-Cao I, Borras C . Delayed ageing through damage protection by the Arf/p53 pathway. Nature. 2007; 448(7151):375-9. DOI: 10.1038/nature05949. View

Yang K, Edelmann W, Fan K, Lau K, Kolli V, Fodde R . A mouse model of human familial adenomatous polyposis. J Exp Zool. 1997; 277(3):245-54. View

Jacks T, Shih T, Schmitt E, Bronson R, Bernards A, Weinberg R . Tumour predisposition in mice heterozygous for a targeted mutation in Nf1. Nat Genet. 1994; 7(3):353-61. DOI: 10.1038/ng0794-353. View

Schmidt-Supprian M, Rajewsky K . Vagaries of conditional gene targeting. Nat Immunol. 2007; 8(7):665-8. DOI: 10.1038/ni0707-665. View

10.

Wallace H, Marques-Kranc F, Richardson M, Luna-Crespo F, Sharpe J, Hughes J . Manipulating the mouse genome to engineer precise functional syntenic replacements with human sequence. Cell. 2007; 128(1):197-209. DOI: 10.1016/j.cell.2006.11.044. View

11.

Donehower L, Harvey M, Slagle B, McArthur M, Montgomery Jr C, Butel J . Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature. 1992; 356(6366):215-21. DOI: 10.1038/356215a0. View

12.

Hill R, Song Y, Cardiff R, Van Dyke T . Selective evolution of stromal mesenchyme with p53 loss in response to epithelial tumorigenesis. Cell. 2005; 123(6):1001-11. DOI: 10.1016/j.cell.2005.09.030. View

13.

Green J, Hudson T . The promise of genetically engineered mice for cancer prevention studies. Nat Rev Cancer. 2005; 5(3):184-98. DOI: 10.1038/nrc1565. View

14.

Su L, Kinzler K, Vogelstein B, Preisinger A, Moser A, Luongo C . Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science. 1992; 256(5057):668-70. DOI: 10.1126/science.1350108. View

15.

Serrano M, Lin A, McCurrach M, Beach D, Lowe S . Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell. 1997; 88(5):593-602. DOI: 10.1016/s0092-8674(00)81902-9. View

16.

Collins F, Rossant J, Wurst W . A mouse for all reasons. Cell. 2007; 128(1):9-13. DOI: 10.1016/j.cell.2006.12.018. View

17.

Artandi S, DePinho R . Mice without telomerase: what can they teach us about human cancer?. Nat Med. 2000; 6(8):852-5. DOI: 10.1038/78595. View

18.

Villa-Morales M, Santos J, Perez-Gomez E, Quintanilla M, Fernandez-Piqueras J . A role for the Fas/FasL system in modulating genetic susceptibility to T-cell lymphoblastic lymphomas. Cancer Res. 2007; 67(11):5107-16. DOI: 10.1158/0008-5472.CAN-06-4006. View

19.

Brannan C, Perkins A, Vogel K, Ratner N, Nordlund M, Reid S . Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues. Genes Dev. 1994; 8(9):1019-29. DOI: 10.1101/gad.8.9.1019. View

20.

Kendall S, Adam S, Counter C . Genetically engineered human cancer models utilizing mammalian transgene expression. Cell Cycle. 2006; 5(10):1074-9. DOI: 10.4161/cc.5.10.2734. View