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