Deletion in Catna2, encoding alpha N-catenin, causes cerebellar and hippocampal lamination defects and impaired startle modulation.

Document Type

Article

Publication Date

2002

Keywords

Base-Sequence, Cadherins, Cerebellum, Comparative-Study, Cytoskeletal-Proteins, Fear, Gene-Deletion, Genetic-Markers, Genotype, Hippocampus, Homozygote, Mice, Mice-Inbred-C3H, Mice-Mutant-Strains, Microsatellite-Repeats, Nerve-Growth-Factors, Purkinje-Cells, RNA-Messenger, Sequence-Tagged-Sites, Startle-Reaction, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Transgenes

First Page

279

Last Page

284

JAX Source

Nat Genet 2002 Jul; 31(3):279-84.

Abstract

Mice homozygous for the cerebellar deficient folia (cdf) mutation are ataxic and have cerebellar hypoplasia and abnormal lobulation of the cerebellum. In the cerebella of cdf/cdf homozygous mice, approximately 40% of Purkinje cells are located ectopically in the white matter and inner granule-cell layer. Many hippocampal pyramidal cells are scattered in the plexiform layers, and those that are correctly positioned are less densely packed than are cells in wild-type mice. We show that fear conditioning and prepulse inhibition of the startle response are also disrupted in cdf/cdf mice. We identify a deletion on chromosome 6 that removes approximately 150 kb in the cdf critical region. The deletion includes part of Catna2, encoding alpha N-catenin, a protein that links the classical cadherins to the neuronal cytoskeleton. Expression of a Catna2 transgene in cdf/cdf mice restored normal cerebellar and hippocampal morphology, prepulse inhibition and fear conditioning. The findings suggest that catenin cadherin cell-adhesion complexes are important in cerebellar and hippocampal lamination and in the control of startle modulation.

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