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Generation and characterization of heritable reciprocal translocations in mice
L Stubbs1, E A Carver, N L Cacheiro
1Life Sciences Division, Oak Ridge National Laboratory, Tennessee 37831-8077, USA.
Abstract:
Reciprocal translocations have provided crucial tools for the localization of genes associated with a variety of human cancers and hereditary diseases. Although heritable translocations are relatively rare in humans, they can be easily induced in mice through exposure of male germ cells at specific spermatogenic stages to different types of radiation and chemicals. Mutagenesis schemes that produce translocations at high frequencies in the progeny of treated males are summarized, and the use of these valuable mutations for analyzing developmental consequences of partial aneuploidy, for identification of mutant genes, and for other purposes is reviewed. Preliminary studies of a large collection of translocation mutants, including several stocks that display dominantly or recessively inherited phenotypes caused by the disruption of critical genes are described. These combined studies demonstrate that several mutagenesis protocols can be used to generate easily mapped, novel mouse mutations with high efficiency and highlight the unique value of reciprocal translocations as tools for gaining access to the biological functions of mammalian genes.
Insights
Reciprocal translocations in mice are induced via radiation or chemicals. These genetic tools efficiently generate mutations for studying gene function and developmental consequences of partial aneuploidy in mammals.
Area of Science:
- Genetics
- Developmental Biology
- Cancer Research
Background:
- Reciprocal translocations are vital for gene localization in human diseases.
- Heritable translocations are rare in humans but inducible in mice.
- Translocations aid in understanding genetic disorders and cancer.
Purpose of the Study:
- To summarize mutagenesis schemes for high-frequency translocation induction in mice.
- To review the application of translocation mutations in genetic and developmental studies.
- To describe preliminary findings from a collection of translocation mutants.
Main Methods:
- Induction of translocations in male mouse germ cells using radiation and chemicals.
- Analysis of progeny from treated males for translocation frequency.
- Phenotypic characterization of generated translocation mutants.
Main Results:
- Several mutagenesis protocols efficiently generate reciprocal translocations in mice.
- Translocation mutants provide tools for analyzing partial aneuploidy consequences.
- Mutations identified display dominant or recessive phenotypes due to gene disruption.
Conclusions:
- Efficient generation of easily mapped mouse mutations using mutagenesis protocols.
- Reciprocal translocations are invaluable for studying mammalian gene function.
- These genetic tools facilitate research into human cancers and hereditary diseases.
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