Dishevelled is one of several segment polarity genes required for the wingless signal transduction pathway in Drosophila. This developmental pathway appears to be conserved in the mouse, where mutations in murine homologs of this pathway result in a variety of specific abnormalities. Three murine Dishevelled genes, Dvl1, Dvl2 and Dvl3, have been isolated. All three Dvl genes are expressed in a similar pattern in embryos and adults. To address the function of these genes during mammalian development, we have generated mice with targeted disruptions of each of the Dvl genes. Mice completely deficient for Dvl1, are viable, fertile and structurally normal. Surprisingly, these mice exhibited reduced social interaction, including differences in whisker-trimming, deficits in nest-building, less huddling contact during home cage sleeping, and subordinate responses in a social dominance test. Sensorimotor gating was abnormal, as measured by deficits in prepulse inhibition of acoustic and tactile startle. Mice homozygous for null alleles of Dvl2 and Dvl3 survive to adulthood and are fertile, but are born in reduced numbers from heterozygous crosses. However, all Dvl1/Dvl2 double homozygotes display a completely open neural tube and exencephaly, demonstrating an essential role for Dvl genes in neural tube closure. Thus, Dvl mutants provide genetic models for aspects of several human psychiatric disorders including autism, schizophrenia, and Tourette syndrome, as well as for neural tube defects.
