International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)

Table of Contents * Complex Genetics * Developmental Genetics * Gene Annotation * Gene Discovery * Genome Sequencing * Functional Genomics * Mutagenesis * Presentations * Verne Chapman Memorial Lecture

DISRUPTION OF THE aN-CATENIN GENE IN CEREBELLAR DEFICIENT FOLIA MUTANT MICE RESULTS IN CEREBELLAR AND HIPPOCAMPAL LAMINATION DEFECTS

Susan Ackerman
The Jackson Laboratory
600 Main Street
Bar Harbor, ME 04609 USA

Co-Authors: Park C, Edgar JH, Longo-Guess CM
Institution: The Jackson Laboratory

Disruption of the aN-catenin gene in cerebellar deficient folia mutant mice results in cerebellar and hippocampal lamination defects

Cerebellar deficient folia (cdf) is a recently identified spontaneous mouse mutation causing ataxia and cerebellar abnormalities. Our results demonstrate that the cdf mutation disrupts the positioning of a specific subset of Purkinje cells during embryonic development, a process known to depend on the extracellular protein reelin, which also regulates migrations in the hippocampus and neocortex. Analysis of cdf"ROSA26 chimeric mice demonstrated that the cdf mutation is intrinsic to Purkinje cells. Consistent with a role for the cdf gene product in reelin signaling, we observed lamination defects in the hippocampus of cdf mutant mice, although neocortical defects were not seen. In addition, ectopic Purkinje cells in cdf/cdf mice express an increased level of Dab1 protein, as previously observed in mice with mutations in genes in the reelin signaling pathway.

We have fine mapped the cdf mutation to a 0.28 cM interval on Chromosome 6. A deletion in cdf mutant mice that removes the last exon of the aN-catenin (Catna2) gene and continues proximally into adjacent DNA was identified. Cerebellar and hippocampal structure was rescued in cdf mutant mice expressing the Catna2 cDNA. Our findings suggest that Catna2 and its associated cadherins function in positioning neurons in the developing cerebellum and hippocampus.