Deletion in Catna2, encoding alpha N-catenin, causes cerebellar and hippocampal lamination defects and impaired startle modulation.
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.
Park
Chankyu
C
The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA.
Falls
William
W
Finger
Jacqueline H
JH
Longo-Guess
Chantal M
CM
Ackerman
Susan L
SL
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
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