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Related Experiment Videos

Genome dynamics in aging mice.

Martijn E T Dollé1, Jan Vijg

  • 1Sam and Ann Barshop Center for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, Texas 78245, USA.

Genome Research
|November 8, 2002
PubMed
Summary
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Large genome rearrangements accumulate in mouse tissues during aging, increasing with age. These DNA changes, often occurring in specific chromosomes, may contribute to the aging process.

Area of Science:

  • Genetics
  • Molecular Biology
  • Aging Research

Background:

  • Detecting spontaneous genome rearrangements in vivo, particularly in postmitotic tissues, is challenging.
  • Previous studies using a lacZ-plasmid reporter mouse model indicated accumulation of large genome rearrangements during aging.
  • These age-related rearrangements were organ-specific, with breakpoints in the reporter locus and elsewhere in the genome.

Purpose of the Study:

  • To physically characterize genome rearrangements in mouse brain, heart, and liver tissues from young and old mice.
  • To identify the location and nature of breakpoints in lacZ-plasmid reporter loci and the mouse genome.
  • To elucidate potential mechanisms and the impact of large genome rearrangements in aging.

Main Methods:

  • Utilized a lacZ-plasmid reporter mouse model.

Related Experiment Videos

  • Analyzed genome rearrangements in brain, heart, and liver tissues of young and old mice.
  • Employed a mouse genome sequence database for physical characterization of 49 genome rearrangements.

    • Main Results:

    • Half of all breakpoints occurred in chromosomes 3 and 4 (carrying reporter clusters), suggesting intrachromosomal deletions or inversions.
    • The other half of breakpoints were randomly located on other chromosomes, indicating translocations.
    • No regions of extended homology were found at the breakpoints, and transposition was also considered.

    Conclusions:

    • Postulated potential mechanisms for the origin of large genome rearrangements in mouse tissues.
    • Highlighted the organ-specific and age-dependent nature of these rearrangements.
    • Predicted the possible impact of these genome rearrangements as a potential cause of aging.