Chung Wen-Chuan, Huang Tzyy-Nan, Hsueh Yi-Ping
Graduate Institute of Life Sciences, National Defense Medical Center, Academia Sinica, Taipei, Taiwan, ROC.
Neurosignals. 2011;19(3):128-41. doi: 10.1159/000327819. Epub 2011 May 13.
CASK-interacting nucleosome assembly protein (CINAP) has been shown to interact with the calcium/calmodulin-dependent serine kinase (CASK) and the T-box transcription factor T-brain-1 (Tbr1) thus modulating the expression of N-methyl-D-aspartic acid receptor subunit 2b (NMDAR2b) in cultured hippocampal neurons. To explore the physiological significance of CINAP in vivo, CINAP knockout mice were generated and subjected to biochemical, anatomical, and behavioral analyses. Unexpectedly, CINAP deletion did not impact NMDAR2b expression, and these CINAP knockout mice were consistently comparable to wild-type littermates in terms of immediate memory (assessed with the Y maze) and associative memory (evaluated by conditioned taste aversion and contextual and auditory fear conditioning). Although CINAP deletion did not obviously influence learning and memory behaviors, CINAP knockout mice exhibited higher locomotor and exploratory activities. Compared with wild-type littermates, the horizontal and vertical movements of the CINAP knockout mice were higher in a novel environment; in home cages, rearing, sniffing, and jumping also occurred more frequently in CINAP knockout mice. These observations suggest that although CINAP deletion in mice does not influence learning and memory behaviors, CINAP is required for restriction of locomotor and exploratory activities.
已证实与CASK相互作用的核小体组装蛋白（CINAP）可与钙/钙调蛋白依赖性丝氨酸激酶（CASK）及T盒转录因子T-brain-1（Tbr1）相互作用，从而调节培养的海马神经元中N-甲基-D-天冬氨酸受体亚基2b（NMDAR2b）的表达。为探究CINAP在体内的生理意义，制备了CINAP基因敲除小鼠并进行生化、解剖及行为分析。出乎意料的是，CINAP缺失并未影响NMDAR2b的表达，并且这些CINAP基因敲除小鼠在即时记忆（通过Y迷宫评估）和联想记忆（通过条件性味觉厌恶以及情境和听觉恐惧条件反射评估）方面与野生型同窝小鼠始终相当。尽管CINAP缺失并未明显影响学习和记忆行为，但CINAP基因敲除小鼠表现出更高的运动和探索活性。与野生型同窝小鼠相比，CINAP基因敲除小鼠在新环境中的水平和垂直运动更多；在饲养笼中，CINAP基因敲除小鼠的站立、嗅探和跳跃也更频繁发生。这些观察结果表明，尽管小鼠中CINAP缺失不影响学习和记忆行为，但CINAP是限制运动和探索活性所必需的。
