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

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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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Figure 1: Startle amplitude, PPI of startle and fear-potentiated startle in cdf/cdf mice (n = 14) and wildtype controls (n = 11).
Figure 2: Identification of a deletion in the cdf critical region.
Figure 3: Truncation of Catna2 in cdf/cdf mice.
Figure 4: Expression of αN-catenin during cerebellar development.
Figure 5: Expression of the Catna2 cDNA rescues the cdf phenotype.
Figure 6: Normal hippocampal synapse formation in cdf/cdf animals.


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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.

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Correspondence to Susan L. Ackerman.

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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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