Abstract：
Rho-associated protein kinase-2 (ROCK2) is a critical player in many cellular processes and was incriminated in cardiovascular and neurological disorders. Recent evidence has shown that non-selective pharmacological blockage of ROCKs ameliorates behavioral alterations in a mouse model of 16p11.2 haploinsufficiency. We had revealed that 16p11.2-deficient mice also display cerebrovascular abnormalities, including endothelial dysfunction. To investigate whether genetic blockage of ROCK2 also exerts beneficial effects on cognition and angiogenesis, we generated mice with both 16p11.2 and Rock2 haploinsufficiency (16p11.2df/+;Rock2+/-). We find that Rock2 heterozygosity on a 16p11.2df/+ background significantly improved recognition memory. Furthermore, brain endothelial cells from 16p11.2df/+;Rock2+/- mice display improved angiogenic capacity compared to cells from 16p11.2df/+ littermates. Overall, this study implicates Rock2 gene as a modulator of 16p11.2-associated alterations, highlighting its potential as a target for treatment of autism spectrum disorders.
摘要：
Rho相关蛋白激酶2（ROCK2）在许多细胞过程中都是至关重要的参与者，并与心血管和神经系统疾病有关。最近的证据表明，ROCK的非选择性药理阻断可改善16p11.2单倍体功能不全小鼠模型的行为改变。我们发现16p11.2缺陷小鼠也表现出脑血管异常，包括内皮功能障碍。为了研究ROCK2的遗传阻断是否也对认知和血管生成产生有益的影响，我们产生了16p11.2和Rock2单倍功能不全的小鼠(16p11.2df/+;Rock2+/-)。我们发现Rock2杂合性在16p11.2df/+背景上显着改善了识别记忆。此外，来自16p11.2df/+的脑内皮细胞;与来自16p11.2df/+的细胞相比,Rock2+/-小鼠显示出改善的血管生成能力。总的来说,这项研究暗示Rock2基因是16p11.2相关改变的调节剂，强调其作为自闭症谱系障碍治疗目标的潜力。
