Use of transgenic mouse models for studying somatic mutations in aging

Hans Jörg Martus, Martijn E.T. Dolle, Jan A. Gossen, Michaël E.T.I. Boerrigter, Jan Vijg

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Theories on the causes of aging, based on the accumulation of somatic mutations in tissues of an organism, were formulated decades ago, but remain insufficiently tested. Transgenic animals, equipped with integrated bacterial reporter genes that can be efficiently rescued from total genomic DNA of all tissues and organs, represent ideal tools for investigating the types and frequencies of spontaneous mutants accumulating during aging. The first of such systems, based on the transgenic integration of bacteriophage lambda shuttle vectors that contain the bacterial lacZ gene as mutational target, was constructed in our laboratory and is now routinely used. Results obtained with this and the related LacI system that are relevant for the somatic mutation theory of aging will be discussed. One conclusion is that, due to the nature of the transgene. lambda-based systems have the disadvantage that deletion type mutations are underrepresented in comparison to point mutations. To overcome those limitations, we constructed a new transgenic mouse model carrying a pUR288 plasmid shuttle vector with the lacZ reporter gene. Some preliminary data obtained with this model serve to illustrate its potential use to extensively test the somatic mutation theory of aging.

Original languageEnglish (US)
Pages (from-to)203-213
Number of pages11
JournalMutation Research DNAging
Volume338
Issue number1-6
DOIs
StatePublished - Oct 1995
Externally publishedYes

ASJC Scopus subject areas

  • Aging
  • Molecular Biology
  • Genetics

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