Roy Snigdha, Zhao Yu, Allensworth Melody, Farook Mohamed F, LeDoux Mark S, Reiter Lawrence T, Heck Detlef H
Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
Behav Neurosci. 2011 Dec;125(6):962-9. doi: 10.1037/a0025920. Epub 2011 Oct 17.
Fragile X syndrome (FXS; MIM #300624), a well-recognized form of inherited human mental retardation is caused, in most cases, by a CGG trinucleotide repeat expansion in the 5'-untranslated region of FMR1, resulting in reduced expression of the fragile X mental retardation protein (FMRP). Clinical features include macroorchidism, anxiety, mental retardation, motor coordination, and speech articulation deficits. The Fmr1 knockout (Fmr1-KO) mouse, a mouse model for FXS, has been shown to replicate the macroorchidism, cognitive deficits, and neuroanatomical abnormalities found in human FXS. Here we asked whether Fmr1-KO mice also display appendicular and oromotor deficits comparable to the ataxia and dysarthric speech seen in FXS patients. We employed standard motor tests for balance and appendicular motor coordination, and used a novel long-term fluid-licking assay to investigate oromotor function in Fmr1-KO mice and their wild-type (WT) littermates. Fmr1-KO mice performed equally well as their WT littermates on standard motor tests, with the exception of a raised-beam task. However, Fmr1-KO mice had a significantly slower licking rhythm than their WT littermates. Deficits in rhythmic fluid-licking in Fmr1-KO mice have been linked to cerebellar pathologies. It is believed that balance and motor coordination deficits in FXS patients are caused by cerebellar neurophathologies. The neuronal bases of speech articulation deficits in FXS patients are currently unknown. It is yet to be established whether similar neuronal circuits control rhythmic fluid-licking pattern in mice and speech articulation movement in humans.
脆性X综合征（FXS；MIM #300624）是一种广为人知的遗传性人类智力障碍形式，在大多数情况下，是由FMR1基因5'非翻译区的CGG三核苷酸重复扩增引起的，导致脆性X智力障碍蛋白（FMRP）表达降低。临床特征包括巨睾症、焦虑、智力障碍、运动协调和言语表达缺陷。Fmr1基因敲除（Fmr1-KO）小鼠是FXS的一种小鼠模型，已被证明可复制人类FXS中发现的巨睾症、认知缺陷和神经解剖学异常。在这里，我们研究Fmr1-KO小鼠是否也表现出与FXS患者所见的共济失调和构音障碍性言语相当的肢体和口面部运动缺陷。我们采用标准运动测试来评估平衡和肢体运动协调，并使用一种新的长期液体舔舐试验来研究Fmr1-KO小鼠及其野生型（WT）同窝小鼠的口面部运动功能。除了一项高架梁任务外，Fmr1-KO小鼠在标准运动测试中的表现与它们的WT同窝小鼠一样好。然而，Fmr1-KO小鼠的舔舐节奏明显比它们的WT同窝小鼠慢。Fmr1-KO小鼠有节奏的液体舔舐缺陷与小脑病变有关。据信，FXS患者的平衡和运动协调缺陷是由小脑神经病变引起的。目前尚不清楚FXS患者言语表达缺陷的神经基础。小鼠中有节奏的液体舔舐模式和人类言语表达运动是否受相似的神经回路控制还有待确定。
