The RBP-Jк protein is a transcription factor that recog-nizes the sequence C(T)GTGGGGA. The RBP-Jк gene is highly conserved in a wide variety of species and the Drosophila homologue has been shown to be identical to Suppressor of Hairless [Su(H)] which plays important roles in the development of the peripheral nervous system. To explore the function of the RBP-Jк gene in mouse embryo-genesis, a mutation was introduced into the functional RBP-Jк gene in embryonic stem (ES) cells by homologous recombination. Null mutant ES cells survived but null mutant mice showed embryonic lethality before 10.5 days of gestation. The mutant mice showed severe growth retar-dation as early as 8.5 days of gestation. Developmental abnormalities, including incomplete turning of the body axis, microencephaly, abnormal placental development, anterior neuropore opening and defective somitogenesis, were observed in the mutant mice at 9.5 days of gestation. RBP-Jк mutant embryos expressed a posterior mesoder-mal marker FGFR1. Their irregularly shaped somites expressed a somite marker gene Mox 1 but failed to express myogenin. The RBP-Jк gene was revealed to be essential for postimplantation development of mice.