Study on recombination signal binding protein ; RBP-Jkappa

克隆Jkappa-RBP基因作为编码与κ型J片段侧翼的免疫球蛋白重组信号序列结合的蛋白质的基因（Jkappa-RS）。然而，该基因的表达不限于淋巴系统。小鼠Jkappa-RBP基因除了与Jkappa-RS结合外，没有发现其他功能，而果蝇Jkappa-RBP基因的同源基因Suppressor of Hairless（Sup（H））突变影响周围神经系统发育，提示Jkappa-RBP基因也参与小鼠神经系统发育。我们已经在胚胎干（ES）细胞中使用同源重组来获得该基因的无效等位基因。从两个ES克隆产生的小鼠嵌合体将突变的等位基因传递给它们的后代。具有一个破坏的Jkappa-RBP等位基因的小鼠没有显示出任何明显的异常。将Jkappa-RBP基因突变的杂合子进行杂交，以评估纯合子后代中Jkappa-RBP缺失的影响。新生小鼠和成年小鼠均为纯合子，表明胚胎期纯合子致死。胚胎的基因型分析表明，纯合子胚胎在妊娠的第8.5至10.5天死亡。9.5天的纯合子胚胎显示：1）神经管前开口，2）不完全转向，3）小脑畸形。

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.