Comprehensive motor testing in Fmr1-KO mice exposes temporal defects in oromotor coordination.
Comprehensive motor testing in Fmr1-KO mice exposes temporal defects in oromotor coordination.
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DOI：
10.1037/a0025920
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发表时间：
2011-12
影响因子：
1.9
通讯作者：
Heck DH
中科院分区：
文献类型：
--
作者：
Roy S;Zhao Y;Allensworth M;Farook MF;LeDoux MS;Reiter LT;Heck DH
脆性X综合征（FXS; MIM #300624），一种公认的遗传性人类智力低下形式，在大多数情况下，由FMR 1的5′-非翻译区中的CGG三核苷酸重复扩增引起，导致脆性X智力低下蛋白（FMRP）的表达减少。临床特征包括巨大睾丸症、焦虑、智力迟钝、运动协调和言语清晰度缺陷。Fmr 1基因敲除（Fmr 1-KO）小鼠是一种FXS小鼠模型，已被证明可复制人类FXS中发现的巨睾丸症、认知缺陷和神经解剖学异常。在这里，我们询问是否Fmr 1-KO小鼠也表现出与FXS患者中观察到的共济失调和构音障碍类似的无意识和听觉缺陷。我们采用标准运动测试的平衡和apapperular运动协调，并使用一种新的长期液体舔试验，以调查orbal功能在Fmr 1-KO小鼠和野生型（WT）同窝出生。在标准运动测试中，Fmr 1-KO小鼠与WT同窝小鼠表现相同，但升高光束任务除外。然而，Fmr 1-KO小鼠的舔体节律明显慢于WT同窝小鼠。Fmr 1-KO小鼠中节律性液体舔的缺陷与小脑病理学有关。据信，FXS患者的平衡和运动协调缺陷是由小脑神经病理学引起的。FXS患者语言清晰度缺陷的神经基础目前尚不清楚。目前还没有确定是否类似的神经回路控制有节奏的液体舔模式在小鼠和人类的语音清晰度运动。
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.