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 αN-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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We thank M. Takeichi for the NCAT5 antibody, T. Lufkin for the IRES-lacZ plasmid; J. Miyazaki for the pCAGGS plasmid; Q.-Y. Zheng for ABR analysis; L. Bechtold, P. Finger and R. Bronson for assistance with electron microscopy; the Microchemistry Facility for DNA sequencing; W. Frankel, P. Nishina and J. Willott for comments on the manuscript; R. Burgess for discussions and J. Smith for figure preparation. This work was supported by a grant from the National Institutes of Health (National Institute of Neurological Disorders and Stroke) to S.L.A., a National Center for Research Resources Center of Biomedical Research Excellence grant, an NIH subcontract to W.A.F., an NIH postdoctoral fellowship to J.H.F., a grant from the Molecular Medicine Research Group Program of the Korean Ministry of Science and Technology to C.P. and an institutional Cancer Center Support Grant from the National Cancer Institute.
The authors declare no competing financial interests.
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Park, C., Falls, W., Finger, J. et al. Deletion in Catna2, encoding αN-catenin, causes cerebellar and hippocampal lamination defects and impaired startle modulation. Nat Genet 31, 279–284 (2002) doi:10.1038/ng908
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