DISRUPTION OF THE MOUSE RBP-J-KAPPA GENE RESULTS IN EARLY EMBRYONIC DEATH

The RBP-JK protein is a transcription factor that recognizes the seque nce C(T)GTGGGGA, The RBP-J kappa gene is highly conserved in a wide va riety of species and the Drosophila homologue has been shown to be ide ntical to Suppressor of Hairless [Su(H)] which plays important roles i n the development of the peripheral nervous system, To explore the fun ction of the RBP-J kappa gene in mouse embryogenesis, a mutation was i ntroduced into the functional RBP-J kappa gene in embryonic stem (ES) cells by homologous recombination, Null mutant ES cells survived but n ull mutant mice showed embryonic lethality before 10.5 days of gestati on, The mutant mice showed severe growth retardation as early as 8.5 d ays of gestation, Developmental abnormalities, including incomplete tu rning of the body axis, microencephaly, abnormal placental development , anterior neuropore opening and defective somitogenesis, were observe d in the mutant mice at 9.5 days of gestation, RBP-J kappa mutant embr yos expressed a posterior mesodermal marker FGFR1. Their irregularly s haped somites expressed a somite marker gene Mox I but failed to expre ss myogenin. The RBP-J kappa gene was revealed to be essential for pos timplantation development of mice.