Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Mouse models for induced genetic instability at endogenous loci

Oncogene volume 22, pages 7000–7010 (2003)Cite this article

Abstract

Exposure to environmental factors and genetic predisposition of an individual may lead individually or in combination to various genetic diseases including cancer. These diseases may be a consequence of genetic instability resulting in large-scale genomic rearrangements, such as DNA deletions, duplications, and translocations. This review focuses on mouse assays detecting genetic instability at endogenous loci. The frequency of DNA deletions by homologous recombination at the pink-eyed unstable (pun) locus is elevated in mice with mutations in ATM, Trp53, Gadd45, and WRN genes and after exposure to carcinogens. Other quantitative in vivo assays detecting loss of heterozygosity events, such as the mammalian spot assay, Dlb-1 mouse and Aprt mouse assays, are also reviewed. These in vivo test systems may predict hazardous effects of an environmental agent and/or genetic predisposition to cancer.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  • Ames BN, McCann J and Yamasaki E . (1975). Mutat. Res., 31, 347–364.

  • Ashby J and Tennant RW . (1991). Mutat. Res., 257, 229–306.

  • Aubrecht J, Rugo R and Schiestl RH . (1995). Carcinogenesis, 16, 2841–2846.

  • Aubrecht J, Secretan MB, Bishop AJ and Schiestl RH . (1999). Carcinogenesis, 20, 2229–2236.

  • Ballabio A, Bardoni B, Guioli S, Basler E and Camerino G . (1990). Genomics, 8, 263–270.

  • Barber R, Plumb MA, Boulton E, Roux I and Dubrova YE . (2002). Proc. Natl. Acad. Sci. USA, 99, 6877–6882.

  • Barlow C, Dennery PA, Shigenaga MK, Smith MA, Morrow JD, Roberts II LJ, Wynshaw-Boris A and Levine RL . (1999). Proc. Natl. Acad. Sci. USA, 96, 9915–9919.

  • Bartsch H, Malaveille C, Camus AM, Martel-Planche G, Brun G, Hautefeuille A, Sabadie N, Barbin A, Kuroki T, Drevon C, Piccoli C and Montesano R . (1980). IARC Sci. Publ., 27, 179–241.

  • Bishop AJ, Kosaras B, Carls N, Sidman RL and Schiestl RH . (2001). Carcinogenesis, 22, 641–649.

  • Bishop AJR, Barlow C, Wynshaw-Boris AJ and Schiestl RH . (2000a). Cancer Res., 60, 395–399.

  • Bishop AJR, Hollander MC, Kosaras B, Sidman RL, Fornace J and Schiestl RH . (2003). (in press).

  • Bishop AJR, Kosaras B, Sidman RL and Schiestl RH . (2000b). Mutat. Res., 457, 31–40.

  • Bodenstein L and Sidman RL . (1987). Dev. Biol., 121, 192–204.

  • Brennan RJ and Schiestl RH . (1996). Mutat. Res., 356, 171–178.

  • Brennan RJ and Schiestl RH . (1997a). Mutagenesis, 12, 215–220.

  • Brennan RJ and Schiestl RH . (1997b). Mutat. Res., 381, 251–258.

  • Brennan RJ and Schiestl RH . (1998a). Mutat. Res., 397, 271–278.

  • Brennan RJ and Schiestl RH . (1998b). Mutat. Res., 403, 65–73.

  • Brennan RJ and Schiestl RH . (1999). Mutat. Res., 430, 37–45.

  • Brennan RJ, Swoboda BE and Schiestl RH . (1994). Mutat. Res., 308, 159–167.

  • Brilliant MH, Gondo Y and Eicher EM . (1991). Science, 252, 566–569.

  • Brooks RA, Gooderham NJ, Edwards RJ, Boobis AR and Winton DJ . (1999). Carcinogenesis, 20, 109–114.

  • Cable J, Jackson IJ and Steel KP . (1995). Mech. Dev., 50, 139–150.

  • Calabretta B, Robberson DL, Barrera-Saldana HA, Lambrou TP and Saunders GF . (1982). Nature, 296, 219–225.

  • Carls N and Schiestl RH . (1994). Mutat. Res., 320, 293–303.

  • Carls N and Schiestl RH . (1999). Carcinogenesis, 20, 2351–2354.

  • Cassidy SB, Gainey AJ and Butler MG . (1989). Am. J. Hum. Genet., 44, 806–810.

  • Cattanach BM . (1971). Chemical Mutagenesis Vol. 2, In: Hollaender A (ed.) Plenum: New York, pp. 535–539.

    Book  Google Scholar 

  • Chance PF, Alderson MK, Leppig KA, Lensch MW, Matsunami N, Smith B, Swanson PD, Odelberg SJ, Disteche CM and Bird TD . (1993). Cell, 72, 143–151.

  • Davidson GE and Dawson GW . (1977). Arch Toxicol., 38, 99–103.

  • De Flora S, Zanacchi P, Camoirano A, Bennicelli C and Badolati GS . (1984). Mutat. Res., 133, 161–198.

  • de Kok AJ, de Knijff P and Mohn GR . (1983). Mutat. Res., 120, 81–89.

  • de la Chapelle A, Herva R, Koivisto M and Aula P . (1981). Hum. Genet., 57, 253–256.

  • de Serres F and Ashby J . 1981. Evaluation of short term tests for carcinogens.

  • Douglas GR, Gingerich JD, Soper LM, Potvin M and Bjarnason S . (1999). Environ. Mol. Mutagen., 34, 190–194.

  • Dubrova YE, Jeffreys AJ and Malashenko AM . (1993). Nat. Genet., 5, 92–94.

  • Engle SJ, Stockelman MG, Chen J, Boivin G, Yum MN, Davies PM, Ying MY, Sahota A, Simmonds HA, Stambrook PJ and Tischfield JA . (1996). Proc. Natl. Acad. Sci. USA, 93, 5307–5312.

  • Fahrig R . (1975). Mol. Gen. Genet., 138, 309–314.

  • Fahrig R . (1977). Arch. Toxicol., 38, 87–98.

  • Fahrig R . (1993). Environ. Health Perspect., 101 (Suppl 3), 257–261.

  • Fan YJ, Wang Z, Sadamoto S, Ninomiya Y, Kotomura N, Kamiya K, Dohi K, Kominami R and Niwa O . (1995). Int. J. Radiat. Biol., 68, 177–183.

  • Galli A and Schiestl RH . (1995). Mol. Gen. Genet., 248, 301–310.

  • Galli A and Schiestl RH . (1996). Mutat. Res., 370, 209–221.

  • Galli A and Schiestl RH . (1998). Genetics, 149, 1235–1250.

  • Gondo Y, Gardner JM, Nakatsu Y, Durham-Pierre D, Deveau SA, Kuper C and Brilliant MH . (1993). Proc. Natl. Acad. Sci. USA, 90, 297–301.

  • Grassi G, Seravalle G, Calhoun DA, Bolla GB, Giannattasio C, Marabini M, Del Bo A and Mancia G . (1994). Circulation, 90, 248–253.

  • Iverson F and Grant DL . (1991). IARC Sci. Publ., 108, 5–29.

  • Jalili T, Murthy GG and Schiestl RH . (1998). Cancer Res., 58, 2633–2638.

  • Ji Y, Eichler EE, Schwartz S and Nicholls RD . (2000). Genome Res., 10, 597–610.

  • Kamsler A, Daily D, Hochman A, Stern N, Shiloh Y, Rotman G and Barzilai A . (2001). Cancer Res., 61, 1849–1854.

  • Khanna KK and Jackson SP . (2001). Nat. Genet., 27, 247–254.

  • Knudson AG . (2001). Nat. Rev. Cancer, 1, 157–162.

  • Kohler SW, Provost GS, Fieck A, Kretz PL, Bullock WO, Sorge JA, Putman DL and Short JM . (1991). Proc. Natl. Acad. Sci. USA, 88, 7958–7962.

  • Kong Y, Usuda N and Nagata T . (1992). Cell Mol. Biol., 38, 263–272.

  • Kurihara S . (1995). Cardiology, 86, 102–107.

  • Lebel M . (2002). Carcinogenesis, 23, 213–216.

  • Ledbetter DH, Riccardi VM, Airhart SD, Strobel RJ, Keenan BS and Crawford JD . (1981). N. Engl. J. Med., 304, 325–329.

  • Lee SA, Dritschilo A and Jung M . (2001). J. Biol. Chem., 276, 11783–11790.

  • Lehrman MA, Schneider WJ, Sudhof TC, Brown MS, Goldstein JL and Russell DW . (1985). Science, 227, 140–146.

  • Levin DE, Hollstein M, Christman MF, Schwiers EA and Ames BN . (1982). Proc. Natl. Acad. Sci. USA, 79, 7445–7449.

  • Liang L, Deng L, Shao C, Stambrook PJ and Tischfield JA . (2000). Environ. Mol. Mutagen., 35, 150–157.

  • Lupski JR . (1998). Trends Genet., 14, 417–422.

  • Lyon MF, King TR, Gondo Y, Gardner JM, Nakatsu Y, Eicher EM and Brilliant MH . (1992). Proc. Natl. Acad. Sci. USA, 89, 6968–6972.

  • Mazzarella R and Schlessinger D . (1998). Genome Res., 8, 1007–1021.

  • McCann J, Choi E, Yamasaki E and Ames BN . (1975). Proc. Natl. Acad. Sci. USA, 72, 5135–5139.

  • Melvold RW . (1971). Mutat. Res., 12, 171–174.

  • Mirsalis JC, Provost GS, Matthews CD, Hamner RT, Schindler JE, O'Loughlin KG, MacGregor JT and Short JM . (1993). Mutagenesis, 8, 265–271.

  • Mitelman F, Johansson B and Mertens F . (2003). http://cgap.nci.nih.gov/Chromosomes/Mitelman.

  • Morrison V and Ashby J . (1994). Mutagenesis, 9, 367–375.

  • Nakayama A, Nguyen MT, Chen CC, Opdecamp K, Hodgkinson CA and Arnheiter H . (1998). Mech. Dev., 70, 155–166.

  • Naylor J, Brinke A, Hassock S, Green PM and Giannelli F . (1993). Hum. Mol. Genet., 2, 1773–1778.

  • Naylor JA, Nicholson P, Goodeve A, Hassock S, Peake I and Giannelli F . (1996). Blood, 87, 3255–3261.

  • Nelis E, Van Broeckhoven C, De Jonghe P, Lofgren A, Vandenberghe A, Latour P, Le Guern E, Brice A, Mostacciouolo ML, Schiavon F, Palau F, Bort S, Upadhyaya M, Rocchi M, Archidiacono N, Mandich P, Bellone E, Silander K, Savontaus ML, Navon R, Goldberg-Stern H, Extivill X, Volpini V, Friedl W, Zerres K, Tyson J, Malcolm S, Holmberg B, Holmgren G, Mariman ECM, Gabreëls-Festen AAWM, Yapijakis C, Vassilopoulos D, Clark C, Haites N, Hilbert P, Van Maldergem L, Rautenstrauss B, Grehl H, Mountford R, Mann K, Bettecken T, Burgunder JM, Hanemann CO, Müller HW, Hertz JM, Schorderet DF, Küntzer T, Wolf C, Kunert E, Muntoni F, Emmerick-Bock P, Orth U and Gal A . (1996). Eur. J. Hum. Genet., 4, 25–33.

  • Niwa O, Fan YJ, Numoto M, Kamiya K and Kominami R . (1996). J. Radiat. Res. (Tokyo), 37, 217–224.

  • Niwa O and Kominami R . (2001). Proc. Natl. Acad. Sci. USA, 98, 1705–1710.

  • Noda Y, Suzuki T, Kohara A, Hasegawa A, Yotsuyanagi T, Hayashi M, Sofuni T, Yamanaka K and Okada S . (2002). Mutat. Res., 513, 205–212.

  • O'Leary LM, Hicks AM, Peters JM and London S . (1991). Am. J. Ind. Med., 20, 17–35.

  • Pentao L, Wise CA, Chinault AC, Patel PI and Lupski JR . (1992). Nat. Genet., 2, 292–300.

  • Peter Y, Rotman G, Lotem J, Elson A, Shiloh Y and Groner Y . (2001). EMBO J., 20, 1538–1546.

  • Potten CS and Loeffler M . (1987). J. Theor. Biol., 127, 381–391.

  • Potten CS and Loeffler M . (1990). Development, 110, 1001–1020.

  • Provost GS, Mirsalis JC, Rogers BJ and Short JM . (1996). Environ. Mol. Mutagen., 28, 342–347.

  • Purandare SM and Patel PI . (1997). Genome. Res., 7, 773–786.

  • Purchase IF, Longstaff E, Ashby J, Styles JA, Anderson D, Lefevre PA and Westwood FR . (1978). Br. J. Cancer, 37, 873–903.

  • Redhead NJ, Selfridge J, Wu CL and Melton DW . (1996). Hum. Gene. Ther., 7, 1491–1502.

  • Reliene R, Bishop AJR, Aubrecht J and Schiestl RH, (in press) Genetic Recombination Protocols: Methods in Molecular Biology Waldman AS (ed.) Humana Press Inc., Cliffton, UK.

  • Rosemblat S, Durham-Pierre D, Gardner JM, Nakatsu Y, Brilliant MH and Orlow SJ . (1994). Proc. Natl. Acad. Sci. USA, 91, 12071–12075.

  • Russell LB . (1977). Arch. Toxicol., 38, 75–85.

  • Russell LB and Major MH . (1957). Genetics, 42, 161–175.

  • Russell LB, Selby PB, von Halle E, Sheridan W and Valcovic L . (1981). Mutat. Res., 86, 355–379.

  • Russell WL, Kelly EM, Hunsicker PR, Bangham JW, Maddux SC and Phipps EL . (1979). Proc. Natl. Acad. Sci. USA, 76, 5818–5819.

  • Sands AT, Suraokar MB, Sanchez A, Marth JE, Donehower LA and Bradley A . (1995). Proc. Natl. Acad. Sci. USA, 92, 8517–8521.

  • Sankaranarayanan K . (1991). Mutat. Res., 258, 3–49.

  • Schichman SA, Caligiuri MA, Strout MP, Carter SL, Gu Y, Canaani E, Bloomfield CD and Croce CM . (1994). Cancer Res., 54, 4277–4280.

  • Schiestl RH . (1989). Nature, 337, 285–288.

  • Schiestl RH, Aubrecht J, Khogali F and Carls N . (1997a). Proc. Natl. Acad. Sci. USA, 94, 4576–4581.

  • Schiestl RH, Aubrecht J, Yap WY, Kandikonda S and Sidhom S . (1997b). Cancer Res., 57, 4378–4383.

  • Schiestl RH, Chan WS, Gietz RD, Mehta RD and Hastings PJ . (1989a). Mutat. Res., 224, 427–436.

  • Schiestl RH, Gietz RD, Mehta RD and Hastings PJ . (1989b). Carcinogenesis, 10, 1445–1455.

  • Schiestl RH, Igarashi S and Hastings PJ . (1988). Genetics, 119, 237–247.

  • Schiestl RH, Khogali F and Carls N . (1994). Science, 266, 1573–1576.

  • Schlager G and Dickie MM . (1967). Genetics, 57, 319–330.

  • Schmid CW, Deka N and Matera AG . (1989). Chromosomes: Eucaryotic, Procaryotic and Viral Vol. I, In: Adolph KW (ed.) CRC Press: Boca Raton, 3–29.

    Google Scholar 

  • Schmidt GH, O'Sullivan JF and Paul D . (1990). Mutat. Res., 228, 149–155.

  • Searle AG . (1977). Arch. Toxicol., 38, 105–108.

  • Shaver-Walker PM, Urlando C, Tao KS, Zhang XB and Heddle JA . (1995). Proc. Natl. Acad. Sci. USA, 92, 11470–11474.

  • Shiraishi K, Shimura T, Taga M, Uematsu N, Gondo Y, Ohtaki M, Kominami R and Niwa O . (2002). Radiat. Res., 157, 661–667.

  • Stambrook PJ, Shao C, Stockelman M, Boivin G, Engle SJ and Tischfield JA . (1996). Environ. Mol. Mutagen., 28, 471–482.

  • Strakowski SM and Butler MG . (1987). Lancet, 2, 1458.

  • Styles JA and Penman MG . (1985). Mutat. Res., 154, 183–204.

  • Takao N, Li Y and Yamamoto K . (2000). FEBS Lett., 472, 133–136.

  • Tao KS, Urlando C and Heddle JA . (1993a). Proc. Natl. Acad. Sci. USA, 90, 10681–10685.

  • Tao KS, Urlando C and Heddle JA . (1993b). Environ. Mol. Mutagen., 22, 293–296.

  • Turker MS, Gage BM, Rose JA, Ponomareva ON, Tischfield JA, Stambrook PJ, Barlow C and Wynshaw-Boris A . (1999). Cancer Res., 59, 4781–4783.

  • van Delft JH, Bergmans A, van Dam FJ, Tates AD, Howard L, Winton DJ and Baan RA . (1998). Mutat. Res., 415, 85–96.

  • Van Sloun PP, Wijnhoven SW, Kool HJ, Slater R, Weeda G, van Zeeland AA, Lohman PH and Vrieling H . (1998). Nucleic Acids Res., 26, 4888–4894.

  • Watters D, Kedar P, Spring K, Bjorkman J, Chen P, Gatei M, Birrell G, Garrone B, Srinivasa P, Crane DI and Lavin MF . (1999). J. Biol. Chem., 274, 34277–34282.

  • Wijnhoven SW, Sonneveld E, Kool HJ, van Teijlingen CM and Vrieling H . (2003). Carcinogenesis, 24, 139–144.

  • Wijnhoven SW, Van Sloun PP, Kool HJ, Weeda G, Slater R, Lohman PH, van Zeeland AA and Vrieling H . (1998). Proc. Natl. Acad. Sci. USA, 95, 13759–13764.

  • Winton DJ, Blount MA and Ponder BA . (1988). Nature, 333, 463–466.

  • Winton DJ, Gooderham NJ, Boobis AR, Davies DS and Ponder BA . (1990). Cancer Res., 50, 7992–7996.

  • Winton DJ, Peacock JH and Ponder BA . (1989). Mutagenesis, 4, 404–406.

  • Wise CA, Garcia CA, Davis SN, Heju Z, Pentao L, Patel PI and Lupski JR . (1993). Am. J. Hum. Genet., 53, 853–863.

  • Yen PH, Li XM, Tsai SP, Johnson C, Mohandas T and Shapiro LJ . (1990). Cell, 61, 603–610.

Download references

Acknowledgements

The study is supported by grants from the National Institute of Environmental Health Sciences, NIH, RO1 Grant No. ES09519, NIEHS KO2 award ES00299 as well as funding from the UCLA Center for Occupational and Environmental Health (to RHS), and a post-graduate research fellowship of the UC Toxic Substances Research and Teaching Program (to RR).

Author information

Authors and Affiliations

  1. Departments of Pathology, Environmental Health and Radiation Oncology, David Geffen School of Medicine and School of Public Health, UCLA, 650 Charles E Young Drive South, Los Angeles, 90024, CA, USA

    Ramune Reliene & Robert H Schiestl

Authors
  1. Ramune Reliene
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert H Schiestl
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert H Schiestl.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reliene, R., Schiestl, R. Mouse models for induced genetic instability at endogenous loci. Oncogene 22, 7000–7010 (2003). https://doi.org/10.1038/sj.onc.1206904

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206904

Keywords

Search

Advanced search

Quick links