Cloning and expression of a novel gene for a protein with leucine-rich repeats in the developing mouse nervous system

In a variety of organisms from yeast to humans, members of the leucine-rich repeat (LRR) family, in which one repeal consists of 24 amino acids and leucine residues appear regularly, have been shown to be involved in protein-protein interactions. In Drosophila, members of this family have significant functions in neural development. It is thus possible that similar molecules play a crucial role in the morphogenesis of the mammalian nervous system. Using a human brain cDNA fragment encoding an LRR as a probe, we have isolated a mouse brain cDNA which encodes a new LRR protein, NLRR-3 protein. The isolated cDNA is 3350 bp long including one open reading frame encoding a protein of 707 amino acids, the deduced amino acid sequence of which has a signal peptide and a transmembrane region. The NLRR-3 protein also contains an RGD sequence and 11 LRRs with amino- and carboxy-terminal LRR-flanking regions which are conserved among adhesive proteins and signal-transducing receptors in this family. Northern-blot analysis revealed strong expression of an approx. 4.2 kb NLRR-3 mRNA in the brain from E17 to P7 and weak expression in adults. There in situ hybridization analysis demonstrated that NLRR-3 mRNA was expressed in the brain, in which stronger expression was localized in the ventricular zone and anlage of thalamus, spinal cord, and dorsal root ganglion in E11-17 cerebellum, and cerebral cortex in adults. The molecular structure in addition to the transient and localized expression suggests that the NLRR-3 protein plays a role in the development and maintenance of the nervous system by protein-protein interactions.