Description of Invention:
Genetic factors are important modifiers of a variety of simple and complex behaviors in virtually all organisms. Genetic effects have been inferred from inbred strain analysis in rodents and from linkage analysis in rodents and humans. More recently, genes influencing specific behaviors have been identified by analyzing behavioral abnormalities in mice with targeted gene disruption.
In the present invention, mice completely deficient for Dvl1, a mouse homolog of the Drosophila segment polarity gene Dishevelled, were created by gene targeting. These mice demonstrate that Dvl1 participates in complex behaviors in mammals. Dvl1-deficient mice exhibit 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. In addition, Dvl1-deficient mice display striking abnormalities in sensorimotor gating, as indicated by attenuation of prepulse startle inhibition in the mutant mice. Prepulse inhibition is abnormal in several human neuropsychiatric disorders including schizophrenia, schizotypal personality disorders, obsessive-compulsive disorders, Huntington's disease, and Tourette syndrome. In addition, many of these disorders (as well as autism) are characterized by abnormal social interaction. Hence, Dvl1-deficient mice provide a genetic animal model of aspects of several human psychiatric disorders and serve as a useful model for screening drugs that modify abnormal social interaction and sensorimotor gating.
Potential Area of Application:
Genetic animal model for investigating psychiatric disorders
Animal model for screening behavior-modifying therapeutics
Inventors:
AJ Wynshaw-Boris (NHGRI) N Lijam (NHGRI) R Paylor (NIMH) J Crawley (NIMH) et al.
Patent Status:
DHHS Reference No. E-100-1997/0 -- Research Tool
Relevant Publication: N Lijam, R. Paylor, MP McDonald, JN Crawley, CX Deng, K Herrup, KE Stevens, G Maccaferri, CJ McBain, DJ Sussman, A Wynshaw-Boris, "Social Interaction and Sensorimotor Gating Abnormalities in Mice Lacking DVl1," Cell 1997 Sep 5;90(5):895-905.
Portfolios: Central Nervous System
Central Nervous System -Research Materials-Transgenics Central Nervous System -Research Materials
For Additional Information Please Contact: Tara L. Kirby Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301)435-4426
Email: tarak@mail.nih.gov
Fax: (301)402-0220
