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Tractable Cre-lox system for stochastic alteration of genes in mice

Ashleigh J Miller1, Sandra D Dudley, Jen-Lan Tsao

  • 1Molecular and Medical Genetics, L103, Oregon Health & Science University, 3181 Sam Jackson Park Road, Portland, Oregon 97239, USA.

Nature Methods
|February 12, 2008
PubMed

Insights

We created a new mouse model for studying cancer development. This cell division-activated Cre-lox system allows researchers to track gene mutations as they occur, aiding in understanding neoplasia and aging effects.

Area of Science:

  • Genetics and Genomics
  • Developmental Biology
  • Cancer Research

Background:

  • Spontaneous mutations are crucial in cancer development and aging.
  • Tracking the precise timing and location of genetic alterations in vivo is challenging.
  • Existing models often lack the ability to mimic the stochastic nature of early mutational events.

Purpose of the Study:

  • To develop a novel genetic tool for inducing stochastic recombination in a cell-division-dependent manner.
  • To model spontaneous, cancer-causing mutations within specific cellular contexts in mice.
  • To facilitate the study of neoplasia pathways and the consequences of gene alterations during development and aging.

Main Methods:

  • Development of a Cre-lox recombination system activated by cell division.
  • Utilizing frameshift reversion as the trigger for Cre activation.
  • Modulating Cre activation based on DNA mismatch-repair status.
  • Application in mouse models to observe stochastic recombination events.

Main Results:

  • Successfully established a cell division-activated Cre-lox system for stochastic recombination.
  • Demonstrated that Cre activation is influenced by DNA mismatch-repair status.
  • Observed recombination occurring in individual cells within normal tissue, mimicking early mutational events.
  • The system enables visualization of gene alterations in a spatially and temporally controlled manner.

Conclusions:

  • The developed Cre-lox system provides a powerful tool for studying the initiation and progression of neoplasia.
  • This system is valuable for investigating the role of specific gene alterations in development and aging.
  • It offers a unique approach to model spontaneous mutations and their impact on cellular and tissue homeostasis.

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