Genetic mapping of the rat mutation creeping and evaluation of its positional candidate gene reelin

Abstract.

We have previously described a rat autosomal recessive mutation, creeping (cre), causing severe ataxia and disarrangement of neuronal cells in the central nervous system. The mutant strain has recently been successfully inbred, named Komeda Zucker creeping (KZC) rat. In the present study, we have performed a genetic analysis of the creeping mutation, and mapped it to rat Chromosome (Chr) 4. Comparative mapping, together with the similarity of the phenotype, suggested that the creeping mutation is homologous to the mouse reeler mutation. In fact, reelin expression was markedly reduced in the homozygous mutant (cre/cre) animals compared with the normal littermates. Thus, the KZC rat should become a useful biological model with a novel mutation in the reelin gene.