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Mouse models for induced genetic instability at endogenous loci.
Ramune Reliene1, Robert H Schiestl
1Department of Pathology, David Geffen School of Medicine and School of Public Health, UCLA, 650 Charles E Young Drive South, Los Angeles, CA 90024, USA.
Oncogene
|October 15, 2003
Summary
Mouse assays detect genetic instability, a key factor in cancer development. These tests can identify genetic predispositions and environmental risks for cancer.
Area of Science:
- Genetics
- Toxicology
- Cancer Research
Background:
- Genetic diseases, including cancer, arise from environmental factors and genetic predisposition.
- Genetic instability, manifesting as genomic rearrangements like deletions and duplications, underlies these diseases.
- Mouse models provide crucial in vivo systems for studying genetic instability.
Purpose of the Study:
- To review mouse assays that detect genetic instability at endogenous loci.
- To highlight the utility of these assays in identifying cancer predispositions and environmental hazards.
Main Methods:
- Focus on the pink-eyed unstable (p(un)) locus assay for detecting DNA deletions via homologous recombination.
- Review other quantitative in vivo assays, including the mammalian spot assay, Dlb-1 mouse assay, and Aprt mouse assay, for loss of heterozygosity events.
Main Results:
- Elevated DNA deletion frequency at the p(un) locus observed in mice with mutations in ATM, Trp53, Gadd45, and WRN genes.
- Increased deletion frequency also noted after exposure to carcinogens.
- These assays quantitatively measure genetic instability in vivo.
Conclusions:
- In vivo mouse assays are effective tools for detecting genetic instability.
- These systems can predict the carcinogenic potential of environmental agents.
- Mouse assays aid in understanding individual genetic predisposition to cancer.