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.

  • Original Paper
  • Published:

Developmental defects and tumor predisposition in Rb mutant mice

Oncogene volume 18, pages 5293–5303 (1999)Cite this article

Abstract

Targeted gene disruption in the mouse germline permits the introduction of gene mutations similar to those found in inherited human diseases. New advances in gene targeting that enable cell type specific gene disruption in mice further increases the utility of mouse models to study genetic defects as found in cancer. Here we review the phenotypes observed in mice carrying germline mutated copies of the retinoblastoma tumor suppressor gene. We will illustrate how methods that permit tissue-specific Rb inactivation in mice provide new and more versatile tools to gain insight into the etiology of sporadic 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

Similar content being viewed by others

References

  • Agah R, Kirshenbaum LA, Abdellatif M, Truong LD, Chakraborty S, Michael LH and Schneider MD. . 1997 J. Clin. Invest. 100: 2722–2728.

  • al-Ubaidi MR, Font RL, Quiambao AB, Keener MJ, Liou GI, Overbeek PA and Baehr W. . 1992a J. Cell Biol. 119: 1681–1687.

  • al-Ubaidi MR, Hollyfield JG, Overbeek PA and Baehr W. . 1992b Proc. Natl. Acad. Sci. USA 89: 1194–1198.

  • al-Ubaidi MR, Mangini NJ, Quiambao AB, Myers KM, Abler AS, Chang CJ, Butel JS and Hollyfield JG. . 1997 Exp. Eye Res. 64: 573–585.

  • Bader JL, Miller RW, Meadows AT, Zimmerman LE, Champion LA and Voute PA. . 1980 Lancet 2: 582–583.

  • Balmain A and Nagase H. . 1998 Trends Genet. 14: 139–144.

  • Bates S, Phillips AC, Clark PA, Stott F, Peters G, Ludwig RL and Vousden KH. . 1998 Nature 395: 124–125.

  • Bernards R. . 1997 Biochim. Biophys. Acta 1333: 33–40.

  • Bignon YJ, Chen Y, Chang CY, Riley DJ, Windle JJ, Mellon PL and Lee WH. . 1993 Genes Dev. 7: 1654–1662.

  • Bookstein R. . 1994 J. Cell. Biochem. (Suppl). 19: 217–223.

  • Bouffler SD, Kemp CJ, Balmain A and Cox R. . 1995 Cancer Res. 55: 3883–3889.

  • Brehm A, Miska EA, McCance DJ, Reid JL, Bannister AJ and Kouzarides T. . 1998 Nature 391: 597–601.

  • Bremner R, Du DC, Connolly-Wilson MJ, Bridge P, Ahmad KF, Mostachfi H, Rushlow D, Dunn JM and Gallie BL. . 1997 Am. J. Hum. Genet. 61: 556–570.

  • Carter-Dawson LD and LaVail MM. . 1979 J. Comp. Neurol. 188: 263–272.

  • Castano E, Kleyner Y and Dynlacht BD. . 1998 Mol. Cell. Biol. 18: 5380–5391.

  • Chen J, Gorman JR, Stewart V, Williams B, Jacks T and Alt FW. . 1993 Curr. Biol. 3: 405–413.

  • Chen PL, Riley DJ, Chen Y and Lee WH. . 1996 Genes Dev. 10: 2794–2804.

  • Cheng M, Olivier P, Diehl JA, Fero M, Roussel MF, Roberts JM and Sherr CJ. . 1999 EMBO J. 18: 1572–1583.

  • Christensen JB and Imperiale MJ. . 1995 J. Virol. 69: 3945–3948.

  • Clarke AR, Robanus-Maandag E, van Roon M, van der Lugt NM, van der Valk M, Hooper ML, Berns A and te Riele H. . 1992 Nature 359: 328–330.

  • Cobrinik D, Lee MH, Hannon G, Mulligan G, Bronson RT, Dyson N, Harlow E, Beach D, Weinberg RA and Jacks T. . 1996 Genes Dev. 10: 1633–1644.

  • Coxon AB, Ward JM, Geradts J, Otterson GA, Zajac-Kaye M and Kaye FJ. . 1998 Oncogene 17: 1625–1628.

  • Cryns VL, Thor A, Xu HJ, Hu SX, Wierman ME, Vickery Jr AL, Benedict WF and Arnold A. . 1994 N. Engl. J. Med. 330: 757–761.

  • Deng G, Lu Y, Zlotnikov G, Thor AD and Smith HS. . 1996 Science 274: 2057–2059.

  • Di Cunto F, Topley G, Calautti E, Hsiao J, Ong L, Seth PK and Dotto GP. . 1998 Science 280: 1069–1072.

  • Donehower LA, Godley LA, Aldaz CM, Pyle R, Shi YP, Pinkel D, Gray J, Bradley A, Medina D and Varmus HE. . 1995 Genes Dev. 9: 882–895.

  • Dymecki SM. . 1996 Proc. Natl. Acad. Sci. USA 93: 6191–6196.

  • Dyson N. . 1998 Genes Dev. 12: 2245–2262.

  • Eng C, Li FP, Abramson DH, Ellsworth RM, Wong FL, Goldman MB, Seddon J, Tarbell N and Boice Jr JD. . 1993 J. Natl. Cancer Inst. 85: 1121–1128.

  • Fung KM, Chikaraishi DM, Suri C, Theuring F, Messing A, Albert DM, Lee VM and Trojanowski JQ. . 1994 Lab. Invest. 70: 114–124.

  • Gallie BL, Campbell C, Devlin H, Duckett A and Squire JA. . 1999 Cancer Res. 59: 1731–1735.

  • Ghebranious N and Donehower LA. . 1998 Oncogene 17: 3385–3400.

  • Gomez Lahoz E, Liegeois NJ, Zhang P, Engelman JA, Horner J, Silverman A, Burde R, Roussel MF, Sherr CJ, Elledge SJ and DePinho RA. . 1999 Mol. Cell. Biol. 19: 353–363.

  • Grana X, Garriga J and Mayol X. . 1998 Oncogene 17: 3365–3383.

  • Griep AE, Krawcek J, Lee D, Liem A, Albert DM, Carabeo R, Drinkwater N, McCall M, Sattler C, Lasudry JG and Lambert PF. . 1998 Invest. Ophthalmol. Vis. Sci. 39: 2723–2732.

  • Hall M and Peters G. . 1996 Adv. Cancer Res. 68: 67–108.

  • Hamel PA, Phillips RA, Muncaster M and Gallie BL. . 1993 FASEB J. 7: 846–854.

  • Hammang JP, Behringer RR, Baetge EE, Palmiter RD and Brinster RL. . 1993 Neuron 10: 1197–1209.

  • Hanspal M and Hanspal JS. . 1994 Blood 84: 3494–3504.

  • Harbour JW, Lai SL, Whang-Peng J, Gazdar AF, Minna JD and Kaye FJ. . 1988 Science 241: 353–357.

  • Harvey M, McArthur MJ, Montgomery CJ, Bradley A and Donehower LA. . 1993a FASEB J. 7: 938–943.

  • Harvey M, Sands AT, Weiss RS, Hegi ME, Wiseman RW, Pantazis P, Giovanella BC, Tainsky MA, Bradley A and Donehower LA. . 1993b Oncogene 8: 2457–2467.

  • Harvey M, Vogel H, Lee EY, Bradley A and Donehower LA. . 1995 Cancer Res. 55: 1146–1151.

  • Hooper ML. . 1998 EMBO J. 17: 6783–6789.

  • Hooper ML. . 1999 Br. J. Cancer 79: 1273–1276.

  • Horowitz JM, Park SH, Bogenmann E, Cheng JC, Yandell DW, Kaye FJ, Minna JD, Dryja TP and Weinberg RA. . 1990 Proc. Natl. Acad. Sci. USA 87: 2775–2779.

  • Howes KA, Lasudry JG, Albert DM and Windle JJ. . 1994a Invest. Ophthalmol. Vis. Sci. 35: 342–351.

  • Howes KA, Ransom N, Papermaster DS, Lasudry JG, Albert DM and Windle JJ. . 1994b Genes Dev. 8: 1300–1310.

  • Hsieh JK, Fredersdorf S, Kouzarides T, Martin K and Lu X. . 1997 Genes Dev. 11: 1840–1852.

  • Hu N, Gulley ML, Kung JT and Lee EY. . 1997 Cancer Res. 57: 4123–4129.

  • Hu N, Gutsmann A, Herbert DC, Bradley A, Lee WH and Lee EY. . 1994 Oncogene 9: 1021–1027.

  • Hurford Jr RK, Cobrinik D, Lee MH and Dyson N. . 1997 Genes Dev. 11: 1447–1463.

  • Ito M, Mishima H, Inai K, Ito T and Akiyama M. . 1994 Int. J. Oncol. 4: 1329–1332.

  • Jacks T. . 1996 Ann. Rev. Genet. 30: 603–636.

  • Jacks T, Fazeli A, Schmitt EM, Bronson RT, Goodell MA and Weinberg RA. . 1992 Nature 359: 295–300.

  • Jakobiec FA, Tso MO, Zimmerman LE and Danis P. . 1977 Cancer 39: 2048–2058.

  • Jones JM, Attardi L, Godley LA, Laucirica R, Medina D, Jacks T, Varmus HE and Donehower LA. . 1997 Cell Growth Differ. 8: 829–838.

  • Kamijo T, Weber JD, Zambetti G, Zindy F, Roussel MF and Sherr CJ. . 1998 Proc. Natl. Acad. Sci. USA 95: 8292–8297.

  • Kamijo T, Zindy F, Roussel MF, Quelle DE, Downing JR, Ashmun RA, Grosveld G and Sherr CJ. . 1997 Cell 91: 649–659.

  • Kanoe H, Nakayama T, Murakami H, Hosaka T, Yamamoto H, Nakashima Y, Tsuboyama T, Nakamura T, Sasaki MS and Toguchida J. . 1998 Anticancer Res. 18: 2317–2321.

  • Knudson AG. . 1971 Proc. Natl. Acad. Sci. USA 68: 820–823.

  • Knudson AG. . 1993 Nature Genet. 5: 103–104.

  • Koh J, Enders GH, Dynlacht BD and Harlow E. . 1995 Nature 375: 506–510.

  • LeCouter JE, Kablar B, Hardy WR, Ying C, Megeney LA, May LL and Rudnicki MA. . 1998a Mol. Cell. Biol. 18: 7455–7465.

  • LeCouter JE, Kablar B, Whyte PF, Ying C and Rudnicki MA. . 1998b Development 125: 4669–4679.

  • Lee EY, Chang CY, Hu N, Wang YC, Lai CC, Herrup K, Lee WH and Bradley A. . 1992 Nature 359: 288–294.

  • Lee EY, Hu N, Yuan SS, Cox LA, Bradley A, Lee WH and Herrup K. . 1994 Genes Dev. 8: 2008–2021.

  • Lee EY, To H, Shew JY, Bookstein R, Scully P and Lee WH. . 1988 Science 241: 218–221.

  • Lee MH, Williams BO, Mulligan G, Mukai S, Bronson RT, Dyson N, Harlow E and Jacks T. . 1996 Genes Dev. 10: 1621–1632.

  • Liou GI, Geng L, al-Ubaidi MR, Matragoon S, Hanten G, Baehr W and Overbeek PA. . 1990 J. Biol. Chem. 265: 8373–8376.

  • Lukas J, Parry D, Aagaard L, Mann DJ, Bartkova J, Strauss M, Peters G and Bartek J. . 1995 Nature 375: 503–506.

  • Lundberg AS and Weinberg RA. . 1998 Mol. Cell. Biol. 18: 753–761.

  • Macleod KF, Hu Y and Jacks T. . 1996 EMBO J. 15: 6178–6188.

  • Maelandsmo GM, Florenes VA, Hovig E, Oyjord T, Engebraaten O, Holm R, Borresen AL and Fodstad O. . 1996 Br. J. Cancer 73: 909–916.

  • Magnaghi-Jaulin L, Groisman R, Naguibneva I, Robin P, Lorain S, Le Villain JP, Troalen F, Trouche D and Harpaz N. . 1998 Nature 391: 601–604.

  • Marcus DM, Brooks SE, Leff G, McCormick R, Thompson T, Anfinson S, Lasudry J and Albert DM. . 1998 Surv. Ophthalmol. 43: 59–70.

  • Marcus DM, Lasudry JG, Carpenter JL, Windle J, Howes KA, al-Ubaidi MR, Baehr W, Overbeek PA, Font RL and Albert DM. . 1996 Invest. Ophthalmol. Vis. Sci. 37: 392–396.

  • Medema RH, Herrera RE, Lam F and Weinberg RA. . 1995 Proc. Natl. Acad. Sci. USA 92: 6289–6293.

  • Meyers EN, Lewandoski M and Martin GR. . 1998 Nature Genet. 18: 136–141.

  • Miyamoto H, Shuin T, Torigoe S, Iwasaki Y and Kubota Y. . 1995 Br. J. Cancer 71: 831–835.

  • Moll AC, Imhof SM, Bouter LM and Tan KE. . 1997 Opthalmic Genet. 18: 27–34.

  • Morgenbesser SD, Williams BO, Jacks T and DePinho RA. . 1994 Nature 371: 72–74.

  • Mulligan G and Jacks T. . 1998 Trends Genet. 14: 223–229.

  • Nikitin AY, Juarez-Perez MI, Li S, Huang L and Lee WH. . 1999 Proc. Natl. Acad. Sci. USA 96: 3916–3921.

  • Nork TM, Poulsen GL, Millecchia LL, Jantz RG and Nickells RW. . 1997 Arch. Ophthalmol. 115: 213–219.

  • Novitch BG, Mulligan GJ, Jacks T and Lassar AB. . 1996 J. Cell Biol. 135: 441–456.

  • Otterson GA, Krazke RA, Coxon A, Kim YW and Kaye FJ. . 1994 Oncogene 9: 3375–3378.

  • Pan H and Griep AE. . 1994 Genes Dev. 8: 1285–1299.

  • Pan H, Yin C, Dyson NJ, Harlow E, Yamasaki L and Van Dyke T. . 1998 Mol. Cell 2: 283–292.

  • Parry D, Mahony D, Wills K and Lees E. . 1999 Mol. Cell. Biol. 19: 1775–1783.

  • Phillips AC, Bates S, Ryan KM, Helin K and Vousden KH. . 1997 Genes Dev. 11: 1853–1863.

  • Pomerantz J, Schreiber-Agus N, Liegeois NJ, Silverman A, Alland L, Chin L, Potes J, Chen K, Orlow I, Lee HW, Cordon-Cardo C and DePinho RA. . 1998 Cell 92: 713–723.

  • Porter A. . 1999 Trends Genet. 14: 73–79.

  • Quelle DE, Cheng M, Ashmun RA and Sherr CJ. . 1997 Proc. Natl. Acad. Sci. USA 94: 669–673.

  • Quelle DE, Zindy F, Ashmun RA and Sherr CJ. . 1995 Cell 83: 993–1000.

  • Rajewsky K, Gu H, Kuhn R, Betz UA, Muller W, Roes J and Schwenk F. . 1996 J. Clin. Invest. 98: 600–603.

  • Rampalli AM, Gao CY, Chauthaiwale VM and Zelenka PS. . 1998 Oncogene 16: 399–408.

  • Riley DJ, Liu CY and Lee WH. . 1997 Mol. Cell. Biol. 17: 7342–7352.

  • Robanus-Maandag E, Dekker M, van der Valk M, Carrozza ML, Jeanny JC, Dannenberg JH, Berns A and te Riele H. . 1998 Genes Dev. 12: 1599–1609.

  • Robanus-Mandag E, van der Valk M, Vlaar M, Feltkamp C, O'Brien J, van Roon M, van der Lugt N, Berns A and te Riele H. . 1994 EMBO J. 13: 4260–4268.

  • Ruas M and Peters G. . 1998 Biochim. Biophys. Acta 1378: F115–F177.

  • Schneider JW, Gu W, Zhu L, Mahdavi V and Nadal-Ginard B. . 1994 Science 264: 1467–1471.

  • Sellers WR, Novitch BG, Miyake S, Heith A, Otterson GA, Kaye FJ, Lassar AB and Kaelin Jr WG. . 1998 Genes Dev. 12: 95–106.

  • Serrano M, Lin AW, McCurrach ME, Beach D and Lowe SW. . 1997 Cell 88: 593–602.

  • Sherr CJ. . 1993 Cell 73: 1059–1065.

  • Sherr CJ. . 1996 Science 274: 1672–1677.

  • Sherr CJ. . 1998 Genes Dev. 12: 2984–2991.

  • Sherr CJ and Roberts JM. . 1995 Genes Dev. 9: 1149–1163.

  • Shibata H, Toyama K, Shioya H, Ito M, Hirota M, Hasegawa S, Matsumoto H, Takano H, Akiyama T, Toyoshima K, Kanamaru R, Kanegae Y, Saito I, Nakamura Y, Shiba K and Noda T. . 1997 Science 278: 120–123.

  • Sicinski P, Donaher JL, Parker SB, Li T, Fazeli A, Gardner H, Haslam SZ, Bronson RT, Elledge SJ and Weinberg RA. . 1995 Cell 82: 621–630.

  • Symonds H, Krall L, Remington L, Saenz RM, Lowe S, Jacks T and Van Dyke T. . 1994 Cell 78: 703–711.

  • Tsai KY, Hu Y, Macleod KF, Crowley D, Yamasaki L and Jacks T. . 1998 Mol. Cell. 2: 293–304.

  • Ueki K, Ono Y, Henson JW, Efird JT, von Deimling A and Louis DN. . 1996 Cancer Res. 56: 150–153.

  • Varley JM, Armour J, Swallow JE, Jeffreys AJ, Ponder BA, T'Ang A, Fung YK, Brammar WJ and Walker RA. . 1989 Oncogene 4: 725–729.

  • Venkatachalam S, Shi YP, Jones SN, Vogel H, Bradley A, Pinkel D and Donehower LA. . 1998 EMBO J. 17: 4657–4667.

  • Vooijs M, van der Valk M, te Riele H and Berns A. . 1998 Oncogene 17: 1–12.

  • Weinberg RA. . 1995 Cell 81: 323–330.

  • Williams BO, Remington L, Albert DM, Mukai S, Bronson RT and Jacks T. . 1994a Nature Genet. 7: 480–484.

  • Williams BO, Schmitt EM, Remington L, Bronson RT, Albert DM, Weinbert RA and Jacks T. . 1994b EMBO J. 13: 4251–4259.

  • Windle JJ, Albert DM, O'Brien JM, Marcus DM, Disteche CM, Bernards R and Mellon PL. . 1990 Nature 343: 665–669.

  • Woo MS, Sanchez I and Dynlacht BD. . 1997 Mol. Cell. Biol. 17: 3566–3579.

  • Yamasaki L. . 1999 Biochim. Biophys. Acta 1423: 9–14.

  • Yamasaki L, Bronson R, Williams BO, Dyson NJ, Harlow E and Jacks T. . 1998 Nature Genet. 18: 360–364.

  • Yamasaki L, Jacks T, Bronson R, Goillot E, Harlow E and Dyson NJ. . 1996 Cell 85: 537–548.

  • Yokoyama T, Liou GI, Caldwell RB and Overbeek PA. . 1992 Exp. Eye Res. 55: 225–233.

  • Young RW. . 1985 Anat. Records 212: 199–205.

  • Zacksenhaus E, Jiang Z, Chung D, Marth JD, Phillips RA and Gallie BL. . 1996 Genes Dev. 10: 3051–3064.

  • Zalvide J and DeCaprio JA. . 1995 Mol. Cell. Biol. 15: 5800–5810.

  • Zhang P, Liegeois NJ, Wong C, Finegold M, Hou H, Thompson JC, Silverman A, Harper JW, DePinho RA and Elledge SJ. . 1997 Nature 387: 151–158.

  • Zhang P, Wong C, DePinho RA, Harper JW and Elledge SJ. . 1998a Genes Dev. 12: 3162–3167.

  • Zhang S, Ramsay ES and Mock BA. . 1998b Proc. Natl. Acad. Sci. USA 95: 2429–2434.

  • Zhang SH, Postigo AA and Dean DC. . 1999 Cell 97: 53–61.

  • Zhang Y, Xiong Y and Yarbrough WG. . 1998c Cell 92: 725–734.

  • Zhu L, Harlow E and Dynlacht BD. . 1995a Genes Dev. 9: 1740–1752.

  • Zhu L, Xie E and Chang LS. . 1995b Mol. Cell. Biol. 15: 3552–3562.

  • Zindy F, Eischen CM, Randle DH, Kamijo T, Cleveland JL, Sherr CJ and Roussel MF. . 1998 Genes Dev. 12: 2424–2433.

  • Zou M, Shi Y, Farid NR and al-Sedairy ST. . 1998 Endocrine 8: 61–64.

Download references

Acknowledgements

The authors wish to thank Hein te Riele and Roderick Beijersbergen for critically reading the manuscript. Our apologies to colleagues whose work could not be directly cited. This work was supported by the Netherlands Organization for Scientific Research (NWO) (M Vooijs) through a program grant to A Berns and by the Dutch Cancer Society (KWF) (A Berns).

Author information

Authors and Affiliations

  1. Division of Molecular Genetics and Centre for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands

    Marc Vooijs & Anton Berns

Authors
  1. Marc Vooijs
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anton Berns
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vooijs, M., Berns, A. Developmental defects and tumor predisposition in Rb mutant mice. Oncogene 18, 5293–5303 (1999). https://doi.org/10.1038/sj.onc.1202999

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1202999

Keywords

This article is cited by

Search

Advanced search

Quick links