Disruption of the mouse RBP-J kappa gene results in early embryonic death.
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 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-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 gestation. The mutant mice showed severe growth retardation 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-J kappa mutant embryos expressed a posterior mesodermal marker FGFR1. Their irregularly shaped somites expressed a somite marker gene Mox 1 but failed to express myogenin. The RBP-J kappa gene was revealed to be essential for postimplantation development of mice.
Oka
C
C
Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Japan.
Nakano
T
T
Wakeham
A
A
de la Pompa
J L
JL
Mori
C
C
Sakai
T
T
Okazaki
S
S
Kawaichi
M
M
Shiota
K
K
Mak
T W
TW
Honjo
T
T
D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D005314:Embryonic and Fetal Development / Q000235:genetics*; D005313:Fetal Death / Q000235:genetics*; D018390:Gene Targeting; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D009420:Nervous System / Q000196:embryology*; D009687:Nuclear Proteins; D013234:Stem Cells / Q000502:physiology*
D004268:DNA-Binding Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D009687:Nuclear Proteins; C497571:Rbpj protein, mouse