Skip to main content
SpringerLink
Log in

Mouse Models of Glioma Pathogenesis: History and State of the Art

  • Chapter
  • First Online:
Emerging Concepts in Neuro-Oncology

Abstract

In this chapter, we describe the evolution of experimental models for brain tumors. Model systems were established as early as the 1920s, when chemical carcinogenesis was used to elicit malignant neoplasms in various tissues or organs, including the central nervous system. A more systematic study of different carcinogens, with a detailed histological analysis, followed in the 1950s and 1960s. At the same time, retroviral carcinogenesis was used as an alternative approach, and refined virus delivery resulted in more realistic models for gliomas. Brain tumors resulting from these approaches were carefully characterized and resembled high-grade gliomas, including oligodendroglial tumors and glioblastomas. The models were limited in that a cell of origin could not be formally demonstrated, but the localization of the lesions suggested that the ventricular zone may have been the origin of some of the tumors. 20 years later, an entirely different approach, the transgenic expression of oncogenic (virus- derived) gene sequences, started a new era of cancer research. These technologies were soon followed by “straight” gene knockout models, and in the mid 1990s, the more refined conditional (Cre-Lox) gene knockout system, which was modified in various ways to allow tissue specific, temporally controlled expression of oncogenes or inactivation of tumor suppressor genes. For the first time, these models led to an in-depth understanding of the mechanisms of brain tumor pathogenesis and the identification of the cells giving rise to intrinsic brain tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Wechsler W, Kleihues P, Matsumot S, Zulch KJ, Ivankovi S, Preussma R. Pathology of experimental neurogenic tumors chemically induced during prenatal and postnatal life. Ann N Y Acad Sci. 1969;159(A2):360.

    Article  Google Scholar 

  2. Swenberg JA. Neoplasms of the nervous system. In: Foster H, Small J, JG F, editors. The mouse in biomedical research. New York: Academic; 1982. p. 529–37.

    Google Scholar 

  3. Fraser H, Mcconnell I. Experimental brain tumors. Lancet. 1975;1(7897):44.

    Article  PubMed  CAS  Google Scholar 

  4. Hayes C, Kelly D, Murayama S, Komiyama A, Suzuki K, Popko B. Expression of the neu oncogene under the transcriptional control of the myelin basic-protein gene in transgenic mice – generation of transformed glial-cells. J Neurosci Res. 1992;31(1):175–87.

    Article  PubMed  CAS  Google Scholar 

  5. Eibl RH, Kleihues P, Jat PS, Wiestler OD. A model for primitive neuroectodermal tumors in transgenic neural transplants harboring the SV40 large T antigen. Am J Pathol. 1994;144(3):556–64.

    PubMed  CAS  Google Scholar 

  6. Cooper JA, Gould KL, Cartwright CA, Hunter T. Tyr527 is phosphorylated in Pp60c-Src – implications for regulation. Science. 1986;231(4744):1431–4.

    Article  PubMed  CAS  Google Scholar 

  7. Brugge J, Cotton P, Lustig A, Yonemoto W, Lipsich L, Coussens P, et al. Characterization of the altered form of the C-Src gene-product in neuronal cells. Genes Dev. 1987;1(3):287–96.

    Article  PubMed  CAS  Google Scholar 

  8. Greenhouse JJ, Petropoulos CJ, Crittenden LB, Hughes SH. Helper-independent retrovirus vectors with Rous-associated virus type-O long terminal repeats. J Virol. 1988;62(12):4809–12.

    PubMed  CAS  Google Scholar 

  9. Hughes SH, Greenhouse JJ, Petropoulos CJ, Sutrave P. Adapter plasmids simplify the insertion of foreign DNA into helper-independent retroviral vectors. J Virol. 1987;61(10):3004–12.

    PubMed  CAS  Google Scholar 

  10. Zhu Y, Guignard F, Zhao D, Liu L, Burns DK, Mason RP, et al. Early inactivation of p53 tumor suppressor gene cooperating with NF1 loss induces malignant astrocytoma. Cancer Cell. 2005;8(2):119–30.

    Article  PubMed  CAS  Google Scholar 

  11. Abremski K, Hoess R. Bacteriophage P1 site-specific recombination. Purification and properties of the cre recombinase protein. J Biol Chem. 1984;259(3):1509–14.

    PubMed  CAS  Google Scholar 

  12. Sternberg N, Hamilton D. Bacteriophage P1 site-specific recombination. I. Recombination between loxP sites. J Mol Biol. 1981;150(4):467–86.

    Article  PubMed  CAS  Google Scholar 

  13. Sternberg N, Hamilton D, Hoess R. Bacteriophage P1 site-specific recombination. II. Recombination between loxP and the bacterial chromosome. J Mol Biol. 1981;150(4):487–507.

    Article  PubMed  CAS  Google Scholar 

  14. Kuhn R, Schwenk F, Aguet M, Rajewsky K. Inducible gene targeting in mice. Science. 1995;269(5229):1427–9.

    Article  PubMed  CAS  Google Scholar 

  15. Di Cristofano A, Pesce B, Cordon-Cardo C, Pandolfi PP. Pten is essential for embryonic development and tumour suppression. Nat Genet. 1998;19(4):348–55.

    Article  PubMed  Google Scholar 

  16. Stambolic V, Suzuki A, de la Pompa JL, Brothers GM, Mirtsos C, Sasaki T, et al. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell. 1998;95(1):29–39.

    Article  PubMed  CAS  Google Scholar 

  17. Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997;275(5308):1943–7.

    Article  PubMed  CAS  Google Scholar 

  18. Su LK, Kinzler KW, Vogelstein B, Preisinger AC, Moser AR, Luongo C, et al. Multiple intestinal neoplasia caused by a mutation in the murine homolog of the Apc gene. Science. 1992;256(5057):668–70.

    Article  PubMed  CAS  Google Scholar 

  19. Ashton-Rickardt PG, Dunlop MG, Nakamura Y, Morris RG, Purdie CA, Steel CM, et al. High frequency of APC loss in sporadic colorectal carcinoma due to breaks clustered in 5q21-22. Oncogene. 1989;4(10):1169–74.

    PubMed  CAS  Google Scholar 

  20. Ichii S, Horii A, Nakatsuru S, Furuyama J, Utsunomiya J, Nakamura Y. Inactivation of both APC alleles in an early stage of colon adenomas in a patient with familial adenomatous polyposis (FAP). Hum Mol Genet. 1992;1(6):387–90.

    Article  PubMed  CAS  Google Scholar 

  21. Holland EC, Hively WP, Gallo V, Varmus HE. Modeling mutations in the G1 arrest pathway in human gliomas: overexpression of CDK4 but not loss of INK4a-ARF induces hyperploidy in cultured mouse astrocytes. Genes Dev. 1998;12(23):3644–9.

    Article  PubMed  CAS  Google Scholar 

  22. Holland EC, Hively WP, DePinho RA, Varmus HE. A constitutively active epidermal growth factor receptor cooperates with disruption of G1 cell-cycle arrest pathways to induce glioma-like lesions in mice. Genes Dev. 1998;12(23):3675–85.

    Article  PubMed  CAS  Google Scholar 

  23. Bates S, Phillips AC, Clark PA, Stott F, Peters G, Ludwig RL, et al. p14ARF links the tumour suppressors RB and p53 [letter]. Nature. 1998;395(6698):124–5.

    Article  PubMed  CAS  Google Scholar 

  24. Palmero I, Pantoja C, Serrano M. p19ARF links the tumour suppressor p53 to Ras. Nature. 1998;395(6698):125–6.

    Article  PubMed  CAS  Google Scholar 

  25. Serrano M, Hannon GJ, Beach D. A new regulatory motif in cell-cycle control causing specific-inhibition of cyclin-D/Cdk4. Nature. 1993;366(6456):704–7.

    Article  PubMed  CAS  Google Scholar 

  26. von Deimling A, von Ammon K, Schoenfeld D, Wiestler OD, Seizinger BR, Louis DN. Subsets of glioblastoma multiforme defined by molecular genetic analysis. Brain Pathol. 1993;3(1):19–26.

    Article  Google Scholar 

  27. Watanabe K, Tachibana O, Sata K, Yonekawa Y, Kleihues P, Ohgaki H. Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas. Brain Pathol. 1996;6(3):217–23. discussion 23–4.

    Article  PubMed  CAS  Google Scholar 

  28. Rabotti GF, Raine WA, Sellers RL. Brain tumors (gliomas ) induced in hamsters by Bryans strain of Rous sarcoma virus. Science. 1965;147(3657):505.

    Article  Google Scholar 

  29. Mennel HD. Significance of experimental models in neurooncology. Neurosurg Rev. 1980;3(2):129–37.

    Article  PubMed  CAS  Google Scholar 

  30. Malkin D, Li FP, Strong LC, Fraumeni Jr JF, Nelson CE, Kim DH, et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms [see comments]. Science. 1990;250(4985):1233–8.

    Article  PubMed  CAS  Google Scholar 

  31. Ohgaki H, Eibl RH, Schwab M, Reichel MB, Mariani L, Gehring M, et al. Mutations of the p53 tumor suppressor gene in neoplasms of the human nervous system. Mol Carcinog. 1993;8(2):74–80.

    Article  PubMed  CAS  Google Scholar 

  32. Levine AJ. p53, the cellular gatekeeper for growth and division. Cell. 1997;88(3):323–31.

    Article  PubMed  CAS  Google Scholar 

  33. Jacks T, Fazeli A, Schmitt EM, Bronson RT, Goodell MA, Weinberg RA. Effects of an Rb mutation in the mouse. Nature. 1992;359(6393):295–300.

    Article  PubMed  CAS  Google Scholar 

  34. Murphree AL, Benedict WF. Retinoblastoma: clues to human oncogenesis. Science. 1984;223(4640):1028–33.

    Article  PubMed  CAS  Google Scholar 

  35. Alvarez Buylla A, Lois C. Neuronal stem cells in the brain of adult vertebrates. Stem Cells. 1995;13(3):263–72.

    Article  PubMed  CAS  Google Scholar 

  36. Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell. 1999;97(6):703–16.

    Article  PubMed  CAS  Google Scholar 

  37. Jacques TS, Swales A, Brzozowski MJ, Henriquez NV, Linehan JM, Mirzadeh Z, et al. Combinations of genetic mutations in the adult neural stem cell compartment determine brain tumour phenotypes. EMBO J. 2010;29(1):222–35.

    Article  PubMed  CAS  Google Scholar 

  38. Jackson EL, Garcia-Verdugo JM, Gil-Perotin S, Roy M, Quinones-Hinojosa A, VandenBerg S, et al. PDGFR alpha-positive B cells are neural stem cells in the adult SVZ that form glioma-like growths in response to increased PDGF signaling. Neuron. 2006;51(2):187–99.

    Article  PubMed  CAS  Google Scholar 

  39. Peers JH. The response of the central nervous system to the application of carcinogenic hydrocarbons: I. Dibenzanthracene. Am J Pathol. 1939;15(2):261–272.3.

    PubMed  CAS  Google Scholar 

  40. Peers JH. The response of the central nervous system to the application of carcinogenic hydrocarbons: II. Methylcholanthrene. Am J Pathol. 1940;16(6):799–816.5.

    PubMed  CAS  Google Scholar 

  41. Seligman AM, Shear M. Studies in carcinogenesis. VIII. Experimental production of brain tumors in mice with methylcholanthrene. Am J Cancer. 1939;37:364–95.

    CAS  Google Scholar 

  42. Zimmerman HM, Arnold H. Experimental brain tumors: II. Tumors produced with benzpyrene. Am J Pathol. 1943;19(6):939–55.

    PubMed  CAS  Google Scholar 

  43. Zimmerman HM, Arnold H. Experimental brain tumors. I. Tumors produced with methylcholanthrene. Cancer Res. 1941;1(12):919.

    CAS  Google Scholar 

  44. Magee PN, Barnes JM. The production of malignant primary hepatic tumours in the rat by feeding dimethylnitrosamine. Br J Cancer. 1956;10(1):114.

    Article  PubMed  CAS  Google Scholar 

  45. Mennel HD, Zulch KJ. Formal pathogenesis of experimentally induced brain tumors. Acta Neuropathol. 1972;21(2):140–53.

    Article  PubMed  CAS  Google Scholar 

  46. Mukai N, Kobayash S, Oguri M. Ultrastructural findings in medulloepitheliomatous neoplasms induced by human adenovirus 12 in rodents. Acta Neuropathol. 1974;28(4):293–304.

    Article  PubMed  CAS  Google Scholar 

  47. Kumanish T, Ikuta F, Yamamoto T. Brain tumors induced by Rous-sarcoma virus, Schmidt-Ruppin strain.3. Morphology of brain tumors induced in adult mice. J Natl Cancer Inst. 1973;50(1):95–109.

    Google Scholar 

  48. Jänisch W, Schreiber D. In: Bigner DD, Swenberg JA, editors. Methods of inducing experimental nervous system tumors: Simian sarcoma virus. Experimental tumors of the central nervous system. Kalamazoo, Michigan: Upjohn Company; 1977. p. 36.

    Google Scholar 

  49. Rabotti GF, Anderson WR, Sellers RL. Oncogenic activity of Mill Hill (Harris) strain of Rous sarcoma virus for hamsters. Nature. 1965;206(4987):946.

    Article  PubMed  CAS  Google Scholar 

  50. Brinster RL, Chen HY, Messing A, Vandyke T, Levine AJ, Palmiter RD. Transgenic mice harboring Sv40 T-antigen genes develop characteristic brain-tumors. Cell. 1984;37(2):367–79.

    Article  PubMed  CAS  Google Scholar 

  51. Palmiter RD, Chen HY, Messing A, Brinster RL. Sv40 Enhancer and large-T antigen are instrumental in development of choroid-plexus tumors in transgenic mice. Nature. 1985;316(6027):457–60.

    Article  PubMed  CAS  Google Scholar 

  52. Weissenberger J, Steinbach JP, Malin G, Spada S, Rulicke T, Aguzzi A. Development and malignant progression of astrocytomas in GFAP-v-src transgenic mice. Oncogene. 1997;14(17):2005–13.

    Article  PubMed  CAS  Google Scholar 

  53. Maddalena AS, Hainfellner JA, Hegi ME, Glatzel M, Aguzzi A. No complementation between TP53 or RB-1 and v-src in astrocytomas of GFAP-v-src transgenic mice. Brain Pathol. 1999;9(4):627–37.

    Article  PubMed  CAS  Google Scholar 

  54. Holland EC, Celestino J, Dai C, Schaefer L, Sawaya RE, Fuller GN. Combined activation of Ras and Akt in neural progenitors induces glioblastoma formation in mice. Nat Genet. 2000;25(1):55–7.

    Article  PubMed  CAS  Google Scholar 

  55. Uhrbom L, Kastemar M, Johansson FK, Westermark B, Holland EC. Cell type-specific tumor suppression by Ink4a and Arf in Kras-induced mouse gliomagenesis. Cancer Res. 2005;65(6):2065–9.

    Article  PubMed  CAS  Google Scholar 

  56. Robinson JP, Vanbrocklin MW, Lastwika KJ, McKinney AJ, Brandner S, Holmen SL. Activated MEK cooperates with Ink4a/Arf loss or Akt activation to induce gliomas in vivo. Oncogene. 2011;30(11):1341–50.

    Article  PubMed  CAS  Google Scholar 

  57. Holmen SL, Williams BO. Essential role for Ras signaling in glioblastoma maintenance. Cancer Res. 2005;65(18):8250–5.

    Article  PubMed  CAS  Google Scholar 

  58. Robinson JP, VanBrocklin MW, Guilbeault AR, Signorelli DL, Brandner S, Holmen SL. Activated BRAF induces gliomas in mice when combined with Ink4a/Arf loss or Akt activation. Oncogene. 2010;29(3):335–44.

    Article  PubMed  CAS  Google Scholar 

  59. Reilly KM, Loisel DA, Bronson RT, McLaughlin ME, Jacks T. Nf1; Trp53 mutant mice develop glioblastoma with evidence of strain-specific effects. Nat Genet. 2000;26(1):109–13.

    Article  PubMed  CAS  Google Scholar 

  60. Xiao A, Wu H, Pandolfi PP, Louis DN, Van Dyke T. Astrocyte inactivation of the pRb pathway predisposes mice to malignant astrocytoma development that is accelerated by PTEN mutation. Cancer Cell. 2002;1(2):157–68.

    Article  PubMed  CAS  Google Scholar 

  61. Xiao A, Yin C, Yang C, Di Cristofano A, Pandolfi PP, Van Dyke T. Somatic induction of Pten loss in a preclinical astrocytoma model reveals major roles in disease progression and avenues for target discovery and validation. Cancer Res. 2005;65(12):5172–80.

    Article  PubMed  CAS  Google Scholar 

  62. Zheng H, Ying H, Yan H, Kimmelman AC, Hiller DJ, Chen AJ, et al. p53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation. Nature. 2008;455(7216):1129–33.

    Article  PubMed  CAS  Google Scholar 

  63. Kwon CH, Zhao D, Chen J, Alcantara S, Li Y, Burns DK, et al. Pten haploinsufficiency accelerates formation of high-grade astrocytomas. Cancer Res. 2008;68(9):3286–94.

    Article  PubMed  CAS  Google Scholar 

  64. Alcantara Llaguno S, Chen J, Kwon CH, Jackson EL, Li Y, Burns DK. Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model. Cancer Cell. 2009;15(1):45–56.

    Article  PubMed  Google Scholar 

  65. Chow LM, Endersby R, Zhu X, Rankin S, Qu C, Zhang J, et al. Cooperativity within and among Pten, p53, and Rb pathways induces high-grade astrocytoma in adult brain. Cancer Cell. 2011;19(3):305–16.

    Article  PubMed  CAS  Google Scholar 

  66. Boorman GA. Brain-tumors in Man and animals – report of a workshop. Environ Health Perspect. 1986;68:155–73.

    Article  Google Scholar 

  67. Fuller C, Helton K, Dalton J, Fouladi M, Kun L, Burger P. Polar spongioblastoma of the spinal cord: a case report. Pediatr Dev Pathol. 2006;9(1):75–80.

    Article  PubMed  Google Scholar 

  68. Brodie BB, Gillette JR, Ladu BN. Enzymatic metabolism of drugs and other foreign compounds. Annu Rev Biochem. 1958;27:427–54.

    Article  PubMed  CAS  Google Scholar 

  69. Druckrey H, Preussmann R, Ivankovic S, Schmahl D. Organotropic carcinogenic effects of 65 various N-nitroso- compounds on BD rats. Z Krebsforsch. 1967;69(2):103–201.

    Article  PubMed  CAS  Google Scholar 

  70. Zimmerman HM. Brain tumors – their incidence and classification in man and their experimental production. Ann N Y Acad Sci. 1969;159(A2):337.

    Article  Google Scholar 

  71. Trentin JJ, Yabe Y, Taylor G. The quest for human cancer viruses. Science. 1962;137(3533):835–41.

    Article  PubMed  CAS  Google Scholar 

  72. Huebner RJ, Rowe WP, Lane WT. Oncogenic effects in hamsters of human adenovirus types 12 and 18. Proc Natl Acad Sci U S A. 1962;48(12):2051.

    Article  PubMed  CAS  Google Scholar 

  73. Rabotti GF, Grove AS, Sellers RL, Anderson WR. Induction of multiple brain tumours (gliomata and leptomeningeal sarcomata) in dogs by Rous sarcoma virus. Nature. 1966;209(5026):884.

    Article  PubMed  CAS  Google Scholar 

  74. Rabotti GF, Sellers RL, Anderson WA. Leptomeningeal sarcomata and gliomata induced in rabbits by Rous sarcoma virus. Nature. 1966;209(5022):524.

    Article  PubMed  CAS  Google Scholar 

  75. Jaenisch R, Mintz B. Simian virus 40 DNA sequences in DNA of healthy adult mice derived from preimplantation blastocysts injected with viral DNA. Proc Natl Acad Sci U S A. 1974;71(4):1250–4.

    Article  PubMed  CAS  Google Scholar 

  76. Green MR. When the products of oncogenes and anti-oncogenes meet. Cell. 1989;56(1):1–3.

    Article  PubMed  CAS  Google Scholar 

  77. Peden KWC, Srinivasan A, Farber JM, Pipas JM. Mutants with changes within or near a hydrophobic region of simian virus-40 large tumor-antigen are defective for binding cellular protein-P53. Virology. 1989;168(1):13–21.

    Article  PubMed  CAS  Google Scholar 

  78. Decaprio JA, Ludlow JW, Figge J, Shew JY, Huang CM, Lee WH, et al. Sv40 Large tumor-antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell. 1988;54(2):275–83.

    Article  PubMed  CAS  Google Scholar 

  79. Ewen ME, Ludlow JW, Marsilio E, Decaprio JA, Millikan RC, Cheng SH, et al. An N-terminal transformation-governing sequence of Sv40 large T-antigen contributes to the binding of both P110rb and a 2nd cellular protein, P120. Cell. 1989;58(2):257–67.

    Article  PubMed  CAS  Google Scholar 

  80. Symonds H, Krall L, Remington L, Saenzrobles M, Lowe S, Jacks T, et al. P53-Dependent apoptosis suppresses tumor-growth and progression in-vivo. Cell. 1994;78(4):703–11.

    Article  PubMed  CAS  Google Scholar 

  81. Gotz W, Theuring F, Schachenmayr W, Korf HW. Midline brain-tumors in Msv-Sv 40-transgenic mice originate from the pineal organ. Acta Neuropathol. 1992;83(3):308–14.

    Article  PubMed  CAS  Google Scholar 

  82. Danks RA, Orian JM, Gonzales MF, Tan SS, Alexander B, Mikoshiba K, et al. Transformation of astrocytes in transgenic mice expressing Sv40 T-antigen under the transcriptional control of the glial fibrillary acidic protein promoter. Cancer Res. 1995;55(19):4302–10.

    PubMed  CAS  Google Scholar 

  83. Theurillat JP, Hainfellner J, Maddalena A, Weissenberger J, Aguzzi A. Early induction of angiogenetic signals in gliomas of GFAP-v-src transgenic mice. Am J Pathol. 1999;154(2):581–90.

    Article  PubMed  CAS  Google Scholar 

  84. Holland EC, Varmus HE. Basic fibroblast growth factor induces cell migration and proliferation after glia-specific gene transfer in mice. Proc Natl Acad Sci U S A. 1998;95(3):1218–23.

    Article  PubMed  CAS  Google Scholar 

  85. Schindler G, Capper D, Meyer J, Janzarik W, Omran H, Herold-Mende C. Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma. Acta Neuropathol. 2011;121(3):397–405.

    Article  PubMed  CAS  Google Scholar 

  86. Moser AR, Shoemaker AR, Connelly CS, Clipson L, Gould KA, Luongo C, et al. Homozygosity for the Min allele of Apc results in disruption of mouse development prior to gastrulation. Dev Dyn. 1995;203(4):422–33.

    Article  PubMed  CAS  Google Scholar 

  87. Oshima M, Oshima H, Kitagawa K, Kobayashi M, Itakura C, Taketo M. Loss of Apc heterozygosity and abnormal tissue building in nascent intestinal polyps in mice carrying a truncated Apc gene. Proc Natl Acad Sci U S A. 1995;92(10):4482–6.

    Article  PubMed  CAS  Google Scholar 

  88. Fodde R, Edelmann W, Yang K, Vanleeuwen C, Carlson C, Renault B, et al. 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.

    Article  PubMed  CAS  Google Scholar 

  89. Suzuki A, de la Pompa JL, Stambolic V, Elia AJ, Sasaki T, Barrantes ID, et al. High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice. Curr Biol. 1998;8(21):1169–78.

    Article  PubMed  CAS  Google Scholar 

  90. Gu H, Zou YR, Rajewsky K. Independent control of immunoglobulin switch recombination at individual switch regions evidenced through Cre-IoxP-mediated gene targeting. Cell. 1993;73(6):1155–64.

    Article  PubMed  CAS  Google Scholar 

  91. Gu H, Marth JD, Orban PC, Mossmann H, Rajewsky K. Deletion of a DNA-polymerase-beta gene segment in T-cells using cell-type-specific gene targeting. Science. 1994;265(5168):103–6.

    Article  PubMed  CAS  Google Scholar 

  92. Kwon CH, Zhu X, Zhang J, Knoop LL, Tharp R, Smeyne RJ, et al. Pten regulates neuronal soma size: a mouse model of Lhermitte-Duclos disease. Nat Genet. 2001;29(4):404–11.

    Article  PubMed  CAS  Google Scholar 

  93. Backman SA, Stambolic V, Suzuki A, Haight J, Elia A, Pretorius J, et al. Deletion of Pten in mouse brain causes seizures, ataxia and defects in soma size resembling Lhermitte-Duclos disease. Nat Genet. 2001;29(4):396–403.

    Article  PubMed  CAS  Google Scholar 

  94. Groszer M, Erickson R, Scripture-Adams D, Lesche R, Trumpp A, Zack JA. Negative regulation of neural stem/progenitor cell proliferation by the pten tumor suppressor gene in vivo. Science. 2001;294(5549):2186–9.

    Article  PubMed  CAS  Google Scholar 

  95. Marino S, Krimpenfort P, Leung C, van der Korput HA, Trapman J, Camenisch I, et al. PTEN is essential for cell migration but not for fate determination and tumourigenesis in the cerebellum. Development. 2002;129(14):3513–22.

    PubMed  CAS  Google Scholar 

  96. Anton M, Graham FL. Site-specific recombination mediated by an adenovirus vector expressing the cre recombinase protein: a molecular switch for control of gene expression. J Virol. 1995;69(8):4600–6.

    PubMed  CAS  Google Scholar 

  97. Kaspar BK, Vissel B, Bengoechea T, Crone S, Randolph-Moore L, Muller R, et al. Adeno-associated virus effectively mediates conditional gene modification in the brain. Proc Natl Acad Sci U S A. 2002;99(4):2320–5.

    Article  PubMed  CAS  Google Scholar 

  98. Ahmed BY, Chakravarthy S, Eggers R, Hermens WT, Zhang JY, Niclou SP, et al. Efficient delivery of Cre-recombinase to neurons in vivo and stable transduction of neurons using adeno-associated and lentiviral vectors. BMC Neurosci. 2004;5:4.

    Article  PubMed  Google Scholar 

  99. Wang H, Xie H, Zhang H, Das SK, Dey SK. Conditional gene recombination by adenovirus-driven Cre in the mouse uterus. Genesis. 2006;44(2):51–6.

    Article  PubMed  CAS  Google Scholar 

  100. Mori T, Tanaka K, Buffo A, Wurst W, Kuhn R, Gotz M. Inducible gene deletion in astroglia and radial glia–a valuable tool for functional and lineage analysis. Glia. 2006;54(1):21–34.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Neuropathology, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK

    Sebastian Brandner M.D., FRCPath

Authors
  1. Sebastian Brandner M.D., FRCPath
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sebastian Brandner M.D., FRCPath .

Editor information

Editors and Affiliations

  1. , Department of Clinical Neurosciences, University of Cambridge, Hills Road, Cambridge, CB2 0QQ, United Kingdom

    Colin Watts

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag London

About this chapter

Cite this chapter

Brandner, S. (2013). Mouse Models of Glioma Pathogenesis: History and State of the Art. In: Watts, C. (eds) Emerging Concepts in Neuro-Oncology. Springer, London. https://doi.org/10.1007/978-0-85729-458-6_6

Download citation

  • DOI: https://doi.org/10.1007/978-0-85729-458-6_6

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-0-85729-457-9

  • Online ISBN: 978-0-85729-458-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation