A PHENOTYPE-BASED SCREEN FOR EMBRYONIC LETHAL MUTATIONS IN THE MOUSE

The genetic pathways that control development of the early mammalian e mbryo have remained poorly understood, in part because the systematic mutant screens that have been so successful in the identification of g enes and pathways that direct embryonic development in Drosophila, Cae norhabditis elegans, and zebrafish have not been applied to mammalian embryogenesis, Here we demonstrate that chemical mutagenesis with ethy lnitrosourea can be combined with the resources of mouse genomics to i dentify new genes that are essential for mammalian embryogenesis. A pi lot screen for abnormal morphological phenotypes of midgestation embry os identified five mutant lines; the phenotypes of four of the lines a re caused by recessive traits that map to single regions of the genome . Three mutant lines display defects in neural tube closure: one is ca used by an allele of the open bl ain (opb) locus, one defines a previo usly unknown locus, and one has a complex genetic basis. Two mutations produce novel early phenotypes and map to regions of the genome not p reviously implicated in embryonic patterning.