Phenotypic Analysis: Assessing Timing of Recessive Prenatal Lethality in Mice

Abstract

Once a recessive mutation has been established in a mouse strain in the heterozygous state, the task of phenotypic analysis of the homozygous mutants can begin. This overview leads you through a sequence of steps to determine whether the homozygous mutants are present at birth or whether the mutation causes prenatal lethality. In the case of a prenatal lethality, the time of death of the mutants, which could occur at any time during pre- or postimplanation development, must be firmly established before further phenotypic analysis. Here, we present a detailed plan to efficiently determine the time of prenatal death of the mutants and provide a guide for developmental landmarks to establish how far they progress during gestation. To determine whether or not homozygous mutants are present or normal at any given time point, it is important to recover a sufficient number of embryos. Examples of a simple Chi square test for Mendelian segregation is provided to establish statistical significance for the genotype/phenotype distribution.