DISRUPTION OF THE MOUSE RBP-J(KAPPA) GENE RESULTS IN EARLY EMBRYONIC DEATH (VOL 121, PG 3291, 1995)

The RBP-J kappa protein is a transcription factor that recognizes the sequence C(T)GTGGGGA, The RBP-J kappa gene is highly conserved in a wi de variety of species and the Drosophila homologue has been shown to b e identical to Suppressor of Hairless [Su(H)] which plays important ro les in the development of the peripheral nervous system. To explore th e function of the RBP-J kappa gene in mouse embryogenesis, a mutation was introduced into the functional RBP-J kappa 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 ge station, The mutant mice showed severe growth retardation as early as 8.5 days of gestation, Developmental abnormalities, including incomple te turning of the body axis, microencephaly, abnormal placental develo pment, anterior neuropore opening and defective somitogenesis, were ob served in the mutant mice at 9.5 days of gestation. RBP-J kappa mutant embryos expressed a posterior mesodermal marker FGFR1, Their irregula rly shaped somites expressed a somite marker gene Mox 1 but failed to express myogenin. The RBP-J kappa gene was revealed to be essential fo r postimplantation development of mice.