Disruptions to the maternally inherited allele UBE3A, encoding for an E3 ubiquitin ligase, leads to the manifestation of Angelman Syndrome (AS). While this disorder is rare, the symptoms are severe and lifelong including but not limited to: intractable seizures, abnormal EEG's, ataxic gait, lack of speech, and most notably an abnormally happy demeanor with easily provoked laughter. Currently, little is known about the neurophysiological underpinnings of UBE3A leading to such globally severe phenotypes. Utilizing the newest AS rat model, comprised of a full UBE3A deletion, we aimed to elucidate novel mechanistic actions and potential therapeutic targets. This report demonstrates for the first time that catalytically active UBE3A protein is detectable within cerebrospinal fluid (CSF) of wild type rats but distinctly absent in AS rat CSF. Microdialysis within the rat hippocampus also showed that UBE3A protein is located in the interstitial fluid of wild type rat brains but absent in AS animals. This protein maintains catalytic activity and appears to be regulated in a dynamic activity‐dependent manner.

中文翻译：

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脑脊液和海马细胞外空间中 UBE3A 蛋白的鉴定表明在突触可塑性中具有潜在的新功能

对编码 E3 泛素连接酶的母系遗传等位基因UBE3A的破坏导致天使综合征 (AS) 的表现。虽然这种疾病很少见，但症状是严重的且终生的，包括但不限于：顽固性癫痫发作、异常脑电图、共济失调步态、缺乏言语，以及最显着的异常快乐的举止和容易激起的笑声。目前，对于导致这种全球严重表型的 UBE3A 的神经生理学基础知之甚少。利用最新的 AS 大鼠模型，由完整的UBE3A组成删除，我们旨在阐明新的机制作用和潜在的治疗靶点。该报告首次证明在野生型大鼠的脑脊液 (CSF) 中可检测到催化活性 UBE3A 蛋白，但在 AS 大鼠 CSF 中明显不存在。大鼠海马内的微透析还显示 UBE3A 蛋白位于野生型大鼠脑的间质液中，但在 AS 动物中不存在。这种蛋白质保持催化活性，并且似乎以动态活性依赖性方式进行调节。