Getting around an Early Lethal Phenotype in Mice with Chimeras

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.