ABERRANT SPLICING OF A MOUSE DISABLED HOMOLOG, MDAB1, IN THE SCRAMBLER MOUSE

Abstract Although accurate long-distance neuronal migration is a cardinal feature of cerebral cortical development, little is known about control of this migration. The scrambler ( scm ) mouse shows abnormal cortical lamination that is indistinguishable from reeler . Genetic and physical mapping of scm identified yeast artificial chromosomes containing an exon of mdab1 , a homolog of Drosophila disabled , which encodes a phosphoprotein that binds nonreceptor tyrosine kinases. mdab1 transcripts showed abnormal splicing in scm homozygotes, with 1.5 kb of intracisternal A particle retrotransposon sequence inserted into the mdab1 coding region in antisense orientation, producing a mutated and truncated predicted protein. Therefore, mdab1 is most likely the scm gene, thus implicating nonreceptor tyrosine kinases in neuronal migration and lamination in developing cerebral cortex.