A targeting vector was constructed to insert the cre/ERT2 coding sequence, a polyadenylation signal and an Frt-flanked neo selection cassette in-frame with the start codon of Notch 2, by homologous recombination in ES cells. This resulted in deletion of most of exon 1. Chimeric males were bred to Flpe-expressing females to remove the selection cassette. Mice homozygous for this allele die embryonically. (J:179632)