Genetic deletions of NCAM and PSA impair circadian function in the mouse.
Genetic deletions of NCAM and PSA impair circadian function in the mouse.
复制标题
NCAM 和 PSA 的基因缺失会损害小鼠的昼夜节律功能。
DOI：
10.1016/s0031-9384(01)00468-1
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发表时间：
2001
影响因子：
2.9
通讯作者：
Glass,JD
中科院分区：
文献类型：
--
作者：
Shen,H;Watanabe,M;Tomasiewicz,H;Glass,JD
成人视交叉上核（SCN）表达神经细胞粘附分子（NCAM），其携带聚唾液酸（PSA），一种控制神经组织中可塑性细胞-细胞相互作用的碳水化合物聚合物。NCAM的三种主要亚型[180（主要PSA载体）、140和120 kDa）的表达随发育和生理状态而变化。在具有不同PSA和NCAM表达的三个转基因突变株中评估了昼夜节律计时功能对NCAM和PSA的需求。其中包括：仅缺乏NCAM 180的NCAMtm 3C 1 w小鼠;缺乏NCAM 180、140和PSA的NCAMtm 1Cwr小鼠;以及缺乏所有NCAM同种型和PSA的NCAMtm 1Cgn小鼠。自发活动被稳定地夹带到12小时的光/暗周期（LD）的NCAMtm 3Ciwand NCAMtm 1Cwr突变体，但不是在NCAMtm 1Cgn突变体，每天的发病和活动的偏移是不规则的或丢失。在恒定黑暗（DD）下，表达PSA的NCAMtm 3Ciwmutants的自由运行的节律性与野生型对照相似，但在大多数缺乏PSA的NCAMtm 1Cwr和NCAMtm 1Cgn突变体中明显被破坏。该分析表明，PSA及其NCAM载体是DD下稳定的自由运行的昼夜节律性所必需的，并且NCAM而不是PSA是与LD同步所需的。值得注意的是，当NCAM 180被删除时，NCAM 140作为PSA载体进行补偿，并且可以承担NCAM 180同种型的其他SCN相关功能。
The adult suprachiasmatic nuclei (SCN) express neural cell adhesion molecule (NCAM) that carries polysialic acid (PSA), a carbohydrate polymer which controls plastic cell–cell interactions in neural tissues. Expression of the three major isoforms of NCAM [180 (principal PSA carrier), 140, and 120 kDa) varies with developmental and physiological state. The requirements for NCAM and PSA in circadian timekeeping function were assessed among three transgenic mutant strains with differing expressions of PSA and NCAM. These included: NCAMtm3Ciwmice lacking only NCAM 180; NCAMtm1Cwrmice lacking NCAM 180, 140, and PSA; and NCAMtm1Cgnmice lacking all NCAM isoforms and PSA. Locomotor activity was stably entrained to a 12-h light/dark cycle (LD) in the NCAMtm3Ciwand NCAMtm1Cwrmutants, but not in NCAMtm1Cgnmutants, where the daily onset and offset of activity were irregular or lost. Under constant darkness (DD), the free-running rhythmicity of the NCAMtm3Ciwmutants expressing PSA was similar to wild-type controls, but was markedly disrupted in the majority of the NCAMtm1Cwrand NCAMtm1Cgnmutants lacking PSA. This analysis indicates that PSA and its NCAM carrier are necessary for stable free-running circadian rhythmicity under DD, and that NCAM, but not PSA, is needed for synchronization to LD. Notably, when NCAM 180 is deleted, NCAM 140 compensates as the PSA carrier, and may assume other SCN-related functions of the NCAM 180 isoform.