Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA.
Sci Rep. 2017 Jan 3;7:39941. doi: 10.1038/srep39941.
The alpha7 nicotinic acetylcholine receptor, encoded by the CHRNA7 gene, has been implicated in various psychiatric and behavioral disorders, including schizophrenia, bipolar disorder, epilepsy, autism, Alzheimer's disease, and Parkinson's disease, and is considered a potential target for therapeutic intervention. 15q13.3 microdeletion syndrome is a rare genetic disorder, caused by submicroscopic deletions on chromosome 15q. CHRNA7 is the only gene in this locus that has been deleted entirely in cases involving the smallest microdeletions. Affected individuals manifest variable neurological and behavioral phenotypes, which commonly include developmental delay/intellectual disability, epilepsy, and autism spectrum disorder. Subsets of patients have short attention spans, aggressive behaviors, mood disorders, or schizophrenia. Previous behavioral studies suggested that Chrna7 deficient mice had attention deficits, but were normal in baseline behavioral responses, learning, memory, and sensorimotor gating. Given a growing interest in CHRNA7-related diseases and a better appreciation of its associated human phenotypes, an in-depth behavioral characterization of the Chrna7 deficient mouse model appeared prudent. This study was designed to investigate whether Chrna7 deficient mice manifest phenotypes related to those seen in human individuals, using an array of 12 behavioral assessments and electroencephalogram (EEG) recordings on freely-moving mice. Examined phenotypes included social interaction, compulsive behaviors, aggression, hyperactivity, anxiety, depression, and somatosensory gating. Our data suggests that mouse behavior and EEG recordings are not sensitive to decreased Chrna7 copy number.
α7 型烟碱型乙酰胆碱受体由 CHRNA7 基因编码，与多种精神和行为障碍有关，包括精神分裂症、双相情感障碍、癫痫、自闭症、阿尔茨海默病和帕金森病等，被认为是治疗干预的潜在靶点。15q13.3 微缺失综合征是一种罕见的遗传疾病，由染色体 15q 上的亚微缺失引起。CHRNA7 是该基因座中唯一在涉及最小微缺失的情况下完全缺失的基因。受影响的个体表现出不同的神经和行为表型，通常包括发育迟缓/智力残疾、癫痫和自闭症谱系障碍。部分患者存在注意力不集中、攻击性行为、情绪障碍或精神分裂症。以前的行为研究表明，Chrna7 缺失小鼠存在注意力缺陷，但在基线行为反应、学习、记忆和感觉运动门控方面正常。鉴于人们对 CHRNA7 相关疾病的兴趣日益增加，以及对其相关人类表型的更好理解，对 Chrna7 缺失小鼠模型进行深入的行为特征分析似乎是谨慎的。本研究旨在使用一系列 12 项行为评估和自由移动小鼠的脑电图 (EEG) 记录，研究 Chrna7 缺失小鼠是否表现出与人类个体相似的表型。检查的表型包括社交互动、强迫行为、攻击行为、多动、焦虑、抑郁和躯体感觉门控。我们的数据表明，小鼠行为和 EEG 记录对 Chrna7 拷贝数减少不敏感。
