Study on recombination signal binding protein ; RBP-Jkappa

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The Jkappa-RBP gene was cloned as the gene which encodes the protein binding to the immunoglobulin recombination signal sequence flanking the kappa-type J segment (Jkappa-RS). However, expression of the gene is not restricted to the lymphoid system. And no functions of mouse Jkappa-RBP other than binding to Jkappa-RS have been found. Meanwhile, the Drosophila homologue of Jkappa-RBP gene turned out to be the gene known as Suppressor of Hairless (Sup(H)) whose mutation affects peripheral nervous system development, suggesting that the Jkappa-RBP gene is also involved in mouse neural development.To elucidate the functions of Jkappa-RBP gene in mice, we have used homologous recombination in embryonic stem (ES) cells to derive null alleles of the gene. Mouse chimeras produced from two ES clones transmitted the mutated allele to their offspring. Mice with one disrupted Jkappa-RBP allele did not show any overt abnormalities. Heterozygotes for the mutation in the Jkappa-RBP gene were intercrossed to assess the effect of the loss of Jkappa-RBP in homozygous offspring. None of the new born and adult mice were homozygotes suggesting homozygous lethality at embryonic stage. Genotype analysis of embryos shows that homozygous embryos die between day 8.5 and 10.5 of gestation. Homozygous embryos of day 9.5 show 1) anterior opening of neural tube, 2) incomplete turning, and 3) microencephaly.