ABSTRACT
The reeler mutation in the mouse maps to proximal chromosome 5 and defines a key gene involved in brain development and evolution. No gene product is known, and the locus is currently being characterized by positional cloning. YAC clones corresponding to the closest markers D5Mit61 and D5Mit72 have been isolated. Cloned extremities of the YAC inserts were used to construct a 1.1-Mb contig, a 700-kb fragment of which was shown to contain the reeler locus. The integrity of the contig was verified by physical mapping on genomic DNA. The classical allele of the reeler mutation was associated with a 150-kb deletion between D5Mit61 and D5Mit72, while no gross chromosomal anomaly was found in the Orleans allele. Candidate coding sequences were isolated to construct a preliminary transcriptional map of the reeler region. Cosmid clones mapping within the rl deletion revealed a large transcript of more than 11 kb, which was present in normal embryonic brain but barely detectable in homozygous rlOrl/rlOrl embryonic brain, suggesting strongly that it corresponds to the reeler transcript.
Subject(s)
Cell Adhesion Molecules, Neuronal/genetics , Chromosomes, Artificial, Yeast , Extracellular Matrix Proteins/genetics , Nerve Tissue Proteins/genetics , Animals , Base Sequence , Chromosome Mapping , DNA Primers , Mice , Mice, Inbred BALB C , Molecular Sequence Data , RNA, Messenger/genetics , Reelin Protein , Restriction Mapping , Sequence Deletion , Serine EndopeptidasesABSTRACT
Genetic distances between reeler (gene symbol rl) and the adjacent loci Pgy-1, Sor, and En-2 on proximal chromosome 5 were estimated using a backcross panel between rlOrl/rlOrl BALB/c and C57 mice. Pgy-1 and Sor are located approximately 7 cM away from and centromeric to reeler, whereas En-2 is located distally, approximately 8 cM from reeler. Backcrosses between rlOrl/rlOrl BALB/c and mice with the T31H translocation showed that the breakpoint is located less than 2 cM from reeler. Together with previous work, these observations suggest the following gene order: Cen-Sor/Pgy-1-rl-T31H-En-2-other loci.
