Aberrant splicing of a mouse disabled homolog, mdab1, in the scrambler mouse.
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.
Ware
M L
ML
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA.
Fox
J W
JW
González
J L
JL
Davis
N M
NM
Lambert de Rouvroit
C
C
Russo
C J
CJ
Chua
S C
SC
Goffinet
A M
AM
Walsh
C A
CA
D000818:Animals; D001483:Base Sequence; D002540:Cerebral Cortex / Q000502:physiology; D005260:Female; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012326:RNA Splicing
C103773:Dab1 protein, mouse; D009419:Nerve Tissue Proteins