J Gresack, C Meyer, J Choe, S Mroziuk, K Kerker, J Beltran, M Kwan, A Ghavami, and S Ramboz
Angelman Syndrome (AS) is a rare genetic neurodevelopmental disorder characterized, in part, by developmental delays, movement impairments, and difficulties with communication and language, the effects of which impact children and adults living with AS. The B6.129S7-Ube3atm1Alb/J (B6-E6-AP) mouse line displays characteristics of Angelman syndrome by knocking out the Ube3a allele in neurons. Here we characterized the phenotypic profile of this model by assessing behavioral performance in both neonatal and adult Ube3a gender mixed mice (wild-type litter mates served as controls). Animals were tested in a battery of behavioral tests starting at birth, including geotaxis (data not show) and ultrasonic vocalizations (USV) wherein Ube3a AS animals exhibited abnormalities. In adulthood, animals were again evaluated in a behavioral battery including open field, NeuroCube gait and grip strength (data not shown) and ultrasonic vocalizations. Decreases in the diversity of the USV repertoire were observed in the Ube3a AS animals in adulthood. Evaluation of protein markers in the Ube3a AS mouse is in progress and results are pending. Finally, the extent to which the aforementioned behavioral phenotype in the Ube3a AS mouse can be rescued by postnatal (P2-3) intervention with a single injection of an antisense oligonucleotide (ASO) was examined with results indicating a partial rescue of the Ube3a phenotype in adulthood on measurements of USV, gait, and exploratory behaviors. The ultimate goal of this work is to identify robust early onset and non-invasive readouts that can be used to determine the efficacy of disease modifying therapies, such as ASOs, for Angelman Syndrome.