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Published on: May 29, 2018
Getting around an Early Lethal Phenotype in Mice with Chimeras
Virginia E Papaioannou1, Richard R Behringer2
1Department of Genetics and Development, Columbia University Medical Center, New York, New York 10032, USA vep1@columbia.edu.
Abstract:
The same gene can have many different functions in different places in the body and/or at different times in development and adult life. Often only one organ or one developmental stage is of particular interest to an investigator. If, however, lethality or severe detrimental effects of a mutation prevent the study of the organ or stage of interest, there are a number of ways to circumvent an early effect. In this overview, we discuss one way of getting around an early lethal phenotype by using chimeras, a method that is also useful for studying the mutant cells in the context of a wild-type host as part of the phenotypic analysis. The composition of chimeras with respect to embryonic cell lineages can be controlled to some extent to produce lineage-restricted chimeras with, for example, mutant cells restricted to certain lineages. Depending on the site of action of the mutant gene, this could result in chimeric "rescue." Details of how to distinguish mutant cells from wild type, an essential part of any chimera experiment, are discussed as well as methods to genotype the chimeras with respect to both component cell types.
Insights
Chimeric animals allow researchers to study gene functions when mutations cause early lethality. This technique enables the analysis of mutant cells within a normal environment, revealing specific gene roles.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Genes can exhibit diverse functions across different tissues and developmental stages.
- Studying specific gene functions can be challenging when mutations result in early lethality or severe detrimental effects.
Purpose of the Study:
- To discuss the utility of chimeras for overcoming early lethal phenotypes in genetic studies.
- To highlight the application of chimeras in analyzing mutant cell behavior within a wild-type host context.
Main Methods:
- Utilizing chimeric animals to circumvent early lethal phenotypes.
- Controlling embryonic cell lineage composition to create lineage-restricted chimeras.
- Employing methods to distinguish between mutant and wild-type cells within chimeras.
- Genotyping chimeras to identify the contribution of each cell type.
Main Results:
- Chimeras provide a viable strategy to investigate the functions of genes that cause early lethality.
- Lineage-restricted chimeras allow for the targeted study of mutant cells in specific tissues or lineages.
- The chimeric approach can lead to the "rescue" of mutant phenotypes depending on the gene's site of action.
- Distinguishing and genotyping chimeric components are crucial for accurate phenotypic analysis.
Conclusions:
- Chimeric animal models are powerful tools for dissecting gene function, particularly when standard mutation analysis is hindered by lethality.
- This method facilitates the in vivo study of mutant cells within a supportive wild-type environment, aiding in understanding gene-specific roles.
- The ability to create lineage-restricted chimeras and accurately analyze their composition enhances the precision of developmental and genetic research.
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