A NOVEL NEUROLOGICAL MUTANT MOUSE, YOTARI, WHICH EXHIBITS REELER-LIKEPHENOTYPE BUT EXPRESSES CR-50 ANTIGEN REELIN/

We present yotari, a novel neurological mutant mouse whose mutation is transmitted in an autosomal recessive manner. The phenotype of yotari is very similar to that of reeler. yotari mutants are recognizable by their unstable gait and tremor and by their early deaths at around th e time of weaning. The cerebella of homozygous yotari are hypoplastic and have no foliation. A molecular and a granular cell layer can be id entified, but Purkinje cells are scattered throughout both the granula r layer and white matter. The laminar structure of the cerebral cortex and the hippocampal formation are also distorted. To test whether the mutated gene in yotari is the reeler gene, reelin, yotari heterozygot es were mated with reeler homozygotes or heterozygotes. The absence of abnormal offspring indicated that the yotari gene is distinct from re elin. Furthermore, expression of mRNA and protein of reelin was verifi ed by Northern blotting and immunohistochemistry using a CR-50 monoclo nal antibody (mAb) which is specific to Reelin, the reelin gene produc t. Although the mutation of several genes, including cyclin-dependent kinase 5 (Cdk 5), p35 and LIS1, 45 kDa subunits of platelet-activating factor acetylhydrolase (PAF-AH) Ib, in Miller-Dieker lissencephaly sy ndrome (MDS) has been reported to cause abnormal laminar structure in the brain, no abnormality was found in yotari by Western blotting with antibodies (Ab's) against these molecules. The close similarity of th e phenotypes of yotari and reeler and the expression of reelin in yota ri may suggest that the gene mutated in yotari encodes a molecule that is on the same signaling pathway as Reelin, the product of reelin. yo tari will provide valuable clues to explore the molecular mechanism of neuronal migration and orderly laminar structure formation of the bra in. (C) 1997 Elsevier Science Ireland Ltd.