Comparative Anatomy and Evolutionary Roles of Reelin

The reelin gene maps to mouse chromosome 5 and human chromosome 7q22 (DeSilva et al., 1997; Royaux et al., 1997). The mouse reelin gene has a large size, about 450kb, principally due to the presence of some very large introns. It is composed of 65 exons, 51 of which encode the eight reelin repeats. At the 3′-terminal portion of the gene, alternative splicing involves the inclusion of a hexanucleotide AGTAAG encoding amino acids Val-Ser, which create a potential phosphorylation site. This sequence is flanked by two introns and considered a bona fide exon (exon 64) (Royaux et al., 1997). The hexanucleotide sequence is evolutionarily conserved, because it is observed in the same relative location in the turtle and lizard cDNA, while the similar sequence AATAAG is present in chick (Lambert de Rouvrait et al., 1999). An alternative, polyadenylated product corresponds to the alternative exon 63a, expressed in the embryonic mouse brain, that codes for a truncated protein lacking the C-terminal region. This alternative mRNA represents between 10 and 25% of total reelin message in the embryonic mouse brain and is most abundant in Cajal-Retzius neurons of the cerebral cortex and hippocampus and in granule cells of the cerebellum; highly similar sequences are also found in human and rat. While reelin mRNA containing the microexon 64 is the major form in the brain of mouse, rat, man, turtle, and lizard, reelin transcripts in liver and kidney lack the hexanucleotide (Lambert de Rouvrait et al., 1999).