Female mice heterozygous for creatine transporter deficiency show moderate cognitive deficits
Female mice heterozygous for creatine transporter deficiency show moderate cognitive deficits
复制标题
DOI：
10.1007/s10545-013-9619-x
复制
发表时间：
2014-01-01
影响因子：
4.2
通讯作者：
Skelton, Matthew R.
中科院分区：
文献类型：
--
作者：
Hautman, Emily R.;Kokenge, Amanda N.;Skelton, Matthew R.
肌酸转运蛋白(CRT)缺乏症(CTD)是一种X连锁疾病，以智能障碍和言语延迟为特征。有报道显示，女性携带者有临床症状。我们已经创造了CRT基因敲除(CRT-/y)小鼠，在这些小鼠中，雄性小鼠表现出严重的认知缺陷，作为这种疾病的模型。这项研究的目的是检查雌性携带者小鼠是否表现出认知缺陷。在雌性CRT+/-小鼠的大脑中，观察到肌酸水平和CRT转录本的减少。CRT+/-小鼠表现出多动，在Morris水迷宫(MWM)中寻找线索平台的潜伏期延长。CRT+/-雌性小鼠在MWM隐藏平台获得方面存在缺陷，但在反转测试中没有。在两个阶段都观察到了探测器试验中的记忆缺陷。雌性CRT+/-小鼠的新物体识别记忆和情境恐惧记忆没有受到影响。雌性CRT+/-小鼠表现出中度认知缺陷，这与人类的一些数据一致。雌性CRT+/-小鼠在进一步了解CTD和测试治疗方法方面可能会被证明是有益的。
Creatine transporter (CrT) deficiency (CTD) is an X-linked disorder characterized by intellectual disability and speech delay. There have been reports that show female carriers have clinical symptoms. We have created CrT knockout (CrT-/y) mice in which males show severe cognitive deficits as a model of this disorder. The purpose of this study was to examine if the female carrier mice show cognitive deficits. Reductions in Cr levels as well as CrT transcript were observed in the brains of the female CrT+/- mice. CrT+/- mice show hyperactivity and increased latency to find the cued platform in the Morris water maze (MWM). CrT+/- female mice showed deficits in MWM hidden platform acquisition but not during reversal testing. Memory deficits on probe trials were observed during both phases. Novel object recognition memory and contextual fear memory were not affected in female CrT+/- mice. Female CrT+/- mice show moderate cognitive deficits, which is consistent with some of the human data. Female CrT+/- mice could prove to be beneficial in further understanding CTD and testing therapeutic approaches.