SHANK3（編碼SHANK3突觸支架蛋白的基因）發(fā)生的突變與自閉癥,、智殘和精神分裂癥有關(guān),，但SHANK3過度表達的效應卻不大清楚。
現(xiàn)在,，Huda Zoghbi及同事發(fā)現(xiàn),，過度表達Shank3的小鼠會表現(xiàn)出類似狂躁的行為以及癲癇發(fā)作和神經(jīng)活動的激發(fā)/抑制平衡發(fā)生改變等。與在小鼠身上的這些發(fā)現(xiàn)相一致的是,，他們識別出了在22號染色體上攜帶含SHANK3區(qū)域的一個基因復本的兩個多動癥患者,。
這些發(fā)現(xiàn)支持以下假設：任何一個方向上（過度表達和表達不足）的不正確基因劑量都可能是有害的。作者提出,，這項研究中所用的小鼠為了解某些形式的躁郁癥的藥物遺傳機理提供了一個模型,。（生物谷Bioon.com）
生物谷推薦的英文摘要
Nature doi:10.1038/nature12630
SHANK3 overexpression causes manic-like behaviour with unique pharmacogenetic properties
Kihoon Han，J. Lloyd Holder Jr,，Christian P. Schaaf,，Hui Lu，Hongmei Chen,，Hyojin Kang,，Jianrong Tang，Zhenyu Wu,，Shuang Hao，Sau Wai Cheung,，Peng Yu,，Hao Sun，Amy M. Breman,，Ankita Patel,，Hui-Chen Lu& Huda Y. Zoghbi
Mutations in SHANK3 and large duplications of the region spanning SHANK3 both cause a spectrum of neuropsychiatric disorders， indicating that proper SHANK3 dosage is critical for normal brain function. However,， SHANK3 overexpression per se has not been established as a cause of human disorders because 22q13 duplications involve several genes. Here we report that Shank3 transgenic mice modelling a human SHANK3 duplication exhibit manic-like behaviour and seizures consistent with synaptic excitatory/inhibitory imbalance. We also identified two patients with hyperkinetic disorders carrying the smallest SHANK3-spanning duplications reported so far. These findings indicate that SHANK3 overexpression causes a hyperkinetic neuropsychiatric disorder. To probe the mechanism underlying the phenotype,， we generated a Shank3 in vivo interactome and found that Shank3 directly interacts with the Arp2/3 complex to increase F-actin levels in Shank3 transgenic mice. The mood-stabilizing drug valproate， but not lithium,， rescues the manic-like behaviour of Shank3 transgenic mice raising the possibility that this hyperkinetic disorder has a unique pharmacogenetic profile.
