ISOLATION OF AN ALLELE OF REELER BY INSERTIONAL MUTAGENESIS

Reeler (rl) is an autosomal recessive mutation that affects migration of postmitotic neurons in the mouse central nervous system. The reeler (rl/rl) mouse displays a disruption of laminar structures in both the cerebellum and the forebrain and it exhibits tremors, dystonia, and a taxia. The molecular basis of the reeler phenotype is unknown because the gene involved has not yet been identified. We report here the isol ation and characterization of an allele of rl, reeler(trangene) (r1(tg )). This allele was generated by the fortuitous insertion of a transge ne, supfos (sf), into the mouse rl locus. Crosses between rl/+ and rl( tg)/+ mice yielded offspring that exhibited the reeler phenotype, indi cating that rl and rl(tg) are allelic. We cloned the genomic sequences flanking the transgene insertion site from the rl(tg)/rl(tg) mouse ge nome. Chromosomal mapping studies revealed that the 5' flanking cellul ar sequence maps to a locus, D5Gmr1, that lies in a region of mouse ch romosome 5 that also contains the rl locus. Southern blot analysis usi ng a probe derived from the D5Gmr1 locus revealed no gross structural rearrangement in the rl locus. Thus, unlike the two rl alleles describ ed previously, rl(tg) provides a molecular probe that can now be used to identify and isolate the rl gene.