A phenotype-based screen for embryonic lethal mutations in the mouse.
The genetic pathways that control development of the early mammalian embryo have remained poorly understood, in part because the systematic mutant screens that have been so successful in the identification of genes and pathways that direct embryonic development in Drosophila, Caenorhabditis elegans, and zebrafish have not been applied to mammalian embryogenesis. Here we demonstrate that chemical mutagenesis with ethylnitrosourea can be combined with the resources of mouse genomics to identify new genes that are essential for mammalian embryogenesis. A pilot screen for abnormal morphological phenotypes of midgestation embryos identified five mutant lines; the phenotypes of four of the lines are caused by recessive traits that map to single regions of the genome. Three mutant lines display defects in neural tube closure: one is caused by an allele of the open brain (opb) locus, one defines a previously unknown locus, and one has a complex genetic basis. Two mutations produce novel early phenotypes and map to regions of the genome not previously implicated in embryonic patterning.
Kasarskis
A
A
Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, and the Sloan-Kettering Division, Graduate School of Medical Sciences, Cornell University, 1275 York Avenue, New York, NY 10021, USA.
Manova
K
K
Anderson
K V
KV
D000818:Animals; D002874:Chromosome Mapping; D004622:Embryo, Mammalian / Q000002:abnormalities*; D005260:Female; D005804:Genes, Lethal; D005808:Genes, Recessive; D005819:Genetic Markers; D005820:Genetic Testing / Q000379:methods*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009154:Mutation; D009436:Neural Tube Defects / Q000175:diagnosis / Q000235:genetics; D010641:Phenotype
D005819:Genetic Markers