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A recombination-based transgenic mouse system for genotoxicity testing

J R Murti1, K J Schimenti, J C Schimenti

  • 1Jackson Laboratory, Bar Harbor, ME 04609.

Mutation Research
|June 1, 1994
PubMed
Summary
This summary is machine-generated.

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Researchers developed a transgenic mouse model to detect gene conversion, a type of genetic recombination. This system efficiently screens for mutagens, identifying chemicals that cause heritable genetic mutations.

Area of Science:

  • Genetics and Molecular Biology
  • Toxicology and Mutagenesis

Background:

  • Mutagens are known to induce genetic recombination in various organisms.
  • The relationship between mutagenicity and recombination, specifically gene conversion, has been utilized in yeast for mutagenicity assays.
  • Existing methods require further development for efficient whole-animal mutagen screening.

Purpose of the Study:

  • To develop and validate a transgenic mouse system for detecting germ-line gene conversion events.
  • To utilize this system as a tool for efficient mutagen screening.
  • To assess the potential of this model for identifying agents causing heritable genetic mutations.

Main Methods:

  • Development of transgenic mice containing two defective lacZ reporter genes regulated by a spermatogenesis-specific promoter.

Related Experiment Videos

  • Intrachromosomal gene conversion events were required for functional lacZ activity.
  • Detection of gene conversion via histochemical staining or flow cytometry of transgenic spermatids.

    • Main Results:

    • The highly mutagenic compound chlorambucil significantly increased the percentage of lacZ-positive spermatids.
    • Acrylamide, a weak genotoxin, did not cause a marked increase in converted spermatids.
    • The system demonstrated sensitivity in distinguishing between mutagenic and non-mutagenic agents.

    Conclusions:

    • Recombination-based transgenic mouse models offer a viable option for rapid, inexpensive, whole-animal mutagen testing.
    • The described mouse system efficiently detects germ-line gene conversion events.
    • This model holds promise for identifying agents capable of causing heritable genetic mutations in humans.