Genomic Organization of the MouseReelinGene

Abstract

Reelin is the protein defective inreelermice, an extensively studied model of brain development. Thereelingene (symbolReln) codes for a protein of the extracellular matrix that contains eight successive repeats of 350 to 390 amino acids. In this work, we describe the genomic structure of the mousereelingene and the 5′-flanking genomic DNA sequences. Thereelingene is composed of 65 exons spread over approximately 450 kb of genomic DNA. We identified differentreelintranscripts, formed by alternative splicing of a microexon as well as by use of two different polyadenylation sites. All splice sites conform to the GT-AG rule, except for the splice donor site of intron 30, which is GC instead of GT. A processed pseudogene is present in intron 42. Its nucleotide sequence is 86% identical to the sequence of the rat RDJ1 cDNA, which codes for a DnaJ-like protein of the Hsp40 family. Comparison of 8 intron positions in mouse and humanreelingenes reveals a highly conserved genomic structure, suggesting a similar structure of the whole gene in both species. We identified two transcription start sites embedded within a CpG. The promoter region contains putative recognition sites for the transcription factors Sp1 and AP2 but lacks TATA and CAAT boxes. The presence of tandemly repeated regions in the Reelin protein suggests that gene duplication events occurred during evolution. By comparison of the amino acid sequences of the eight repeats and the positions of introns, we suggest a model for the evolution of the repeat coding portion of thereelingene from a putative ancestral minigene.