18965
Bidirectional Changes in UBE3A Gene Dosage Reciprocally Regulate Aggression in Mouse Models of Angelman Syndrome and Idic15

Saturday, May 16, 2015: 11:30 AM-1:30 PM
Imperial Ballroom (Grand America Hotel)
M. P. Anderson1,2,3,4, D. Stoppel5 and Y. Nong5, (1)Pathology/Neurology, Harvard Medical School/Beth Israel Deaconess Medical Center, Boston, MA, (2)Pathology, Boston Children's Hospital, Boston, MA, (3)Autism BrainNET, Boston, MA, (4)Children’s Hospital Boston Intellectual and Developmental Disabilities Research Center, Boston, MA, (5)Harvard Medical School/Beth Israel Deaconess Medical Center, Boston, MA
Background:  Reciprocal changes in UBE3A gene dosage cause two neurodevelopmental disorders. Maternally inherited deletions of UBE3A cause Angelman syndrome, characterized by intellectual disability, motor defects, seizures, and a pathognomonic increased social interest. Whereas maternally inherited triplications of UBE3A as in Idic15 Autism underlie the decreased sociability and increased repetitive restrictive behaviors seen in this genetic condition. Increased male aggression is a common comorbidity in the neurodevelopmental disorders but is not widely studied in mouse models. 

Objectives:  To explore whether Ube3a gene dosage regulates aggression-type behaviors.

Methods:   We compared wild-type mice with mice carrying either two extra copies of Ube3a transgene (Ube3a-2x) that model Idic15 or mice with maternal Ube3a knockout (Ube3a-mKO) in the resident intruder paradigm. 

Results:   Aggression was increased in Ube3a-2x and decreased in Ube3a-mKO when compared to wild-type mice. Using additional mouse genetics techniques, we further mapped the aggression trait to a specific brain circuitry. 

Conclusions:   The findings establish that disturbances in Ube3a gene dosage reciprocally regulate aggression behavior in two mouse models of human developmental disorders and identify specific molecular and cellular defects that could underlie the behavioral problem.

See more of: Animal Models
See more of: Animal Models