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Related Experiment Videos

Transgenic mouse models for gonadal tumorigenesis

N A Rahman1, K Kananen Rilianawati, T Paukku

  • 1Department of Physiology, University of Turku, Kiinamyllynkatu, Finland.

Molecular and Cellular Endocrinology
|January 28, 1999
PubMed
Summary

Transgenic mice expressing Simian virus 40 T-antigen develop gonadal tumors dependent on gonadotropins. Gene therapy using Herpes Simplex virus thymidine kinase blocked tumor growth, demonstrating a potential therapeutic strategy.

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Area of Science:

  • Oncology
  • Genetics
  • Endocrinology

Background:

  • Transgenic (TG) techniques enable in vivo disease modeling.
  • Oncogene expression under tissue-specific promoters creates disease models.
  • Gonadal somatic cell tumors are a focus of research.

Purpose of the Study:

  • To create a transgenic mouse model for gonadal somatic cell tumors.
  • To investigate the role of gonadotropins in tumor development.
  • To test gene therapy strategies for gonadal tumors.

Main Methods:

  • Created TG mice expressing Simian virus 40 T-antigen (Tag) under the inhibin alpha-subunit promoter.
  • Crossbred TG mice with hypogonadotropic hpg mice and treated with GnRH antagonist.
  • Developed TG mice expressing Herpes Simplex virus thymidine kinase (HSV-TK) and crossbred with Tag mice.

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  • Treated double mutant mice with antiherpes drugs (acyclovir, gancyclovir).

    • Main Results:

    • TG mice developed ovarian granulosa/theca cell tumors and testicular Leydig cell tumors with 100% penetrance.
    • Tumors were steroidogenically active, producing progesterone and high inhibin levels.
    • Tumorigenesis was gonadotropin-dependent; no tumors formed in gonadotropin-deficient mice.
    • Treatment with antiherpes drugs blocked tumor growth in double mutant mice.

    Conclusions:

    • The developed TG mouse model accurately reflects gonadal somatic cell tumorigenesis.
    • Gonadotropin dependency is crucial for tumor development.
    • HSV-TK gene therapy shows promise for blocking gonadal tumor growth.
    • Immortalized cell lines from these tumors can be used for in vitro functional studies.