Division of Neurology, MLC 7044 Cincinnati Children's Research Foundation, 3333 Burnet Ave., Cincinnati, OH, 45229-3039, USA.
J Inherit Metab Dis. 2014 Jan;37(1):63-8. doi: 10.1007/s10545-013-9619-x. Epub 2013 May 29.
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.
肌酸转运蛋白（CrT）缺乏症（CTD）是一种 X 连锁疾病，其特征是智力残疾和言语迟缓。有报道称女性携带者有临床症状。我们已经创建了 CrT 敲除（CrT(-/y)）小鼠，雄性小鼠表现出严重的认知缺陷，作为该疾病的模型。本研究的目的是检查女性携带者小鼠是否存在认知缺陷。在女性 CrT(+/-)小鼠的大脑中观察到 Cr 水平和 CrT 转录物的减少。CrT(+/-) 小鼠在水迷宫（MWM）中表现出过度活跃和找到提示平台的潜伏期增加。CrT(+/-) 雌性小鼠在 MWM 隐藏平台获得测试中表现出缺陷，但在反转测试中没有。在两个阶段都观察到探针试验中的记忆缺陷。女性 CrT(+/-) 小鼠的新物体识别记忆和情境恐惧记忆不受影响。女性 CrT(+/-) 小鼠表现出中度认知缺陷，与一些人类数据一致。女性 CrT(+/-) 小鼠可能有助于进一步了解 CTD 并测试治疗方法。
