DYSFUNCTION OF THE ORLEANS REELER GENE ARISING FROM EXON SKIPPING DUETO TRANSPOSITION OF A FULL-LENGTH COPY OF AN ACTIVE L1 SEQUENCE INTO THE SKIPPED EXON

We examined the genomic structure of the reeler gene in Orleans reeler mouse mutant, Exon skipping of the reeler gene caused a 220 bp deleti on in the transcript, resulting in a frame shift of the reeler gene wh ich disrupts the 8th EGF-like motif of the reeler product, Surprisingl y, the skipped exon was inserted by the 7104 bp L1 element which carri ed the full-length stretch of the mouse L1 sequence, consisting of a 2 12 bp F-type tandem repeat, open reading frame 1 (ORF1), ORF2, the pol yadenylation signal and a poly A stretch, The transposed L1 sequence w as flanked by 13 bp of the target sequence at both ends, ORF1 and ORF2 of this L1 repeat element are thought to encode a component of the RN P particle and the reverse transcriptase, respectively, Orleans reeler was originally established by spontaneous mutation caused by L1 inser tion, and this L1 sequence is considered to be potentially active for transposition in mouse genome.