title: Deletion in Catna2, encoding alpha N-catenin, causes cerebellar and hippocampal lamination defects and impaired startle modulation.
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.
authors.affiliation: The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA.
authors.forename: Chankyu
authors.initials: C
authors.lastname: Park
authors.forename: William
authors.initials: W
authors.lastname: Falls
authors.forename: Jacqueline H
authors.initials: JH
authors.lastname: Finger
authors.forename: Chantal M
authors.initials: CM
authors.lastname: Longo-Guess
authors.forename: Susan L
authors.initials: SL
authors.lastname: Ackerman
mesh_terms: D000818:Animals; D001483:Base Sequence; D015820:Cadherins / Q000235:genetics; D002531:Cerebellum / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005239:Fear; D017353:Gene Deletion; D005819:Genetic Markers; D005838:Genotype; D006624:Hippocampus / Q000473:pathology / Q000648:ultrastructure; D006720:Homozygote; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D018895:Microsatellite Repeats; D009414:Nerve Growth Factors / Q000235:genetics* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011689:Purkinje Cells / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D013216:Reflex, Startle / Q000235:genetics / Q000502:physiology*; D016324:Sequence Tagged Sites; D019076:Transgenes; D051178:alpha Catenin
chemical_list: C072167:CAT development factor; D015820:Cadherins; C495272:Ctnna1 protein, mouse; C486820:Ctnna2 protein, mouse; D003598:Cytoskeletal Proteins; D005819:Genetic Markers; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D051178:alpha Catenin