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Related Experiment Videos

Random mutagenesis screen for dominant behavioral mutations in mice

P M Nolan1, D Kapfhamer, M Bućan

  • 1Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.

Methods (San Diego, Calif.)
|March 21, 1998
PubMed
Summary

This study explores using chemical mutagens like N-ethyl-N-nitrosourea (ENU) to efficiently screen for dominant mutations in mice. Researchers tested behavioral assays for identifying genetic changes affecting mouse behavior.

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Area of Science:

  • Genetics and Genomics
  • Neuroscience
  • Pharmacology

Background:

  • Large-scale mutagenesis screens are effective in lower model organisms for identifying gene functions.
  • Mouse models are crucial for genetic research, but screening for recessive mutations is costly.
  • Alternative strategies like region-specific mutagenesis or dominant mutation screening are needed for mice.

Purpose of the Study:

  • To describe a pilot screen for dominant visible and behavioral mutations in mice induced by N-ethyl-N-nitrosourea (ENU).
  • To evaluate the efficiency of ENU mutagenesis protocols and assess strain-specific effects.
  • To test the suitability of high-throughput behavioral assays for large-scale screens.

Main Methods:

  • Induced mutations using the chemical mutagen N-ethyl-N-nitrosourea (ENU).

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  • Developed efficient ENU mutagenesis protocols and assessed strain-specific effects on survival and fertility.
  • Tested behavioral screens including circadian wheel running, Porsolt swim test, and prepulse inhibition of acoustic startle response.

    • Main Results:

    • Reported an efficient protocol for ENU mutagenesis with strain-specific differences in sterility period and survival.
    • Demonstrated the feasibility of using behavioral assays for large-scale screens by prescreening G1 progeny.
    • Identified strain-specific differences in response to mutagenesis.

    Conclusions:

    • The study illustrates the feasibility of using ENU mutagenesis and specific behavioral assays for large-scale screens in mice.
    • Efficient protocols and high-throughput screening methods are crucial for identifying novel ENU-induced mutations.
    • Behavioral screens can effectively detect mutations affecting sensorimotor gating and circadian rhythms.