ABNORMAL FEAR RESPONSE AND AGGRESSIVE-BEHAVIOR IN MUTANT MICE DEFICIENT FOR ALPHA-CALCIUM-CALMODULIN KINASE-II
ABNORMAL FEAR RESPONSE AND AGGRESSIVE-BEHAVIOR IN MUTANT MICE DEFICIENT FOR ALPHA-CALCIUM-CALMODULIN KINASE-II
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DOI：
10.1126/science.7939668
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发表时间：
1994-10-14
期刊：
影响因子：
56.9
通讯作者：
TONEGAWA, S
中科院分区：
文献类型：
--
作者：
CHEN, C;RAINNIE, DG;TONEGAWA, S
缺乏编码α-钙-钙调蛋白依赖性激酶II的基因的小鼠（α-CaMKII敲除小鼠）提供了将行为和细胞异常与特定分子损伤联系起来的有希望的工具。杂合子小鼠表现出行为异常的严格限制的综合征，主要包括恐惧反应降低和防御性攻击增加，在没有任何测量的认知缺陷。与杂合子不同，纯合子在所有测试范式中均表现出异常行为。在细胞水平上，细胞外和全细胞膜片钳记录表明，5-羟色胺释放在假定的背中缝核神经元减少。因此，α-CaMKII基因敲除小鼠，特别是杂合子，可以提供一个模型，用于研究涉及恐惧和攻击性的情绪障碍的分子和细胞基础。
Mice deficient for the gene encoding alpha-calcium-calmodulin-dependent kinase II (alpha-CaMKII knockout mice) provide a promising tool to link behavioral and cellular abnormalities with a specific molecular lesion. The heterozygous mouse exhibited a well-circumscribed syndrome of behavioral abnormalities, consisting primarily of a decreased fear response and an increase in defensive aggression, in the absence of any measured cognitive deficits. Unlike the heterozygote, the homozygote displayed abnormal behavior in all paradigms tested. At the cellular level, both extracellular and whole-cell patch clamp recordings indicated that serotonin release in putative serotonergic neurons of the dorsal raphe was reduced. Thus, alpha-CaMKII knockout mice, in particular the heterozygote, may provide a model for studying the molecular and cellular basis underlying emotional disorders involving fear and aggression.