Abnormal dendrite and spine morphology in primary visual cortex in the CGG knock-in mouse model of the fragile X premutation.
Abnormal dendrite and spine morphology in primary visual cortex in the CGG knock-in mouse model of the fragile X premutation.
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DOI：
10.1111/j.1528-1167.2012.03486.x
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发表时间：
2012-06
期刊：
影响因子：
5.6
通讯作者：
Wenzel HJ
中科院分区：
文献类型：
--
作者：
Berman RF;Murray KD;Arque G;Hunsaker MR;Wenzel HJ
脆性 X 智力低下 1 基因 (Fmr1) 在 5'-非翻译区中的 CGG 三核苷酸重复数量具有多态性，重复长度 <45 与典型发育相关，重复长度 >200 导致基因过度甲基化和转录沉默，以及脆性 X 综合征 (FXS) 中的智力低下。 CGG 重复扩展在 55 到 200 之间的个体是脆弱 X 前突变 (PM) 的携带者。 PM 携带者表现出的表型包括焦虑、抑郁、社交恐惧症和记忆缺陷。他们还有患脆性 X 相关震颤/共济失调综合征 (FXTAS) 的风险，这是一种迟发性神经退行性疾病，其特征为震颤、共济失调、认知障碍和神经病理学特征，包括神经元和星形胶质细胞的核内包涵体、浦肯野细胞缺失和白质疾病。然而，人们对 PM 或 FXTAS 中的树突形态知之甚少。因此，我们对 PM 敲入 (KI) 小鼠模型中初级视觉皮层 II/III 层锥体神经元的树突复杂性和树突棘形态进行了高尔基体研究。这些 CGG KI 小鼠在 Fmr1 上携带扩展的 CGG 三核苷酸重复序列，并模拟 PM 和 FXTAS 的许多特征。与野生型（WT）小鼠相比，CGG KI 小鼠的体细胞近端树突分支较少，树突总长度减少，并且较长树突棘的频率较高。 WT 和 KI 小鼠的形态脊柱类型（例如，粗短型、蘑菇型、丝状伪足型）的分布没有差异。这些发现表明，用于模拟 PM 的小鼠视觉皮层中的突触回路存在异常，并表明这种变化可能是携带 PM 的个体以及患有 FXTAS 的个体中发现的神经系统特征的基础。
The fragile X mental retardation 1 gene (Fmr1) is polymorphic for CGG trinucleotide repeat number in the 5′-untranslated region, with repeat lengths <45 associated with typical development and repeat lengths >200 resulting in hypermethylation and transcriptional silencing of the gene and mental retardation in the fragile X Syndrome (FXS). Individuals with CGG repeat expansions between 55 and 200 are carriers of the fragile X premutation (PM). PM carriers show a phenotype that can include anxiety, depression, social phobia, and memory deficits. They are also at risk for developing fragile X–associated tremor/ataxia syndrome (FXTAS), a late onset neurodegenerative disorder characterized by tremor, ataxia, cognitive impairment, and neuropathologic features including intranuclear inclusions in neurons and astrocytes, loss of Purkinje cells, and white matter disease. However, very little is known about dendritic morphology in PM or in FXTAS. Therefore, we carried out a Golgi study of dendritic complexity and dendritic spine morphology in layer II/III pyramidal neurons in primary visual cortex in a knock-in (KI) mouse model of the PM. These CGG KI mice carry an expanded CGG trinucleotide repeat on Fmr1, and model many features of the PM and FXTAS. Compared to wild-type (WT) mice, CGG KI mice showed fewer dendritic branches proximal to the soma, reduced total dendritic length, and a higher frequency of longer dendritic spines. The distribution of morphologic spine types (e.g., stubby, mushroom, filopodial) did not differ between WT and KI mice. These findings demonstrate that synaptic circuitry is abnormal in visual cortex of mice used to model the PM, and suggest that such changes may underlie neurologic features found in individuals carrying the PM as well as in individuals with FXTAS.
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影响因子：
2
作者：
Basuta, Kirin;Narcisa, Vivien;Chavez, Alyssa;Kumar, Madhur;Gane, Louise;Hagerman, Randi;Tassone, Flora
通讯作者：
Tassone, Flora
影响因子：
5.3
作者：
Chonchaiya W;Au J;Schneider A;Hessl D;Harris SW;Laird M;Mu Y;Tassone F;Nguyen DV;Hagerman RJ
通讯作者：
Hagerman RJ
影响因子：
2.9
作者：
Goodrich-Hunsaker, Naomi J;Wong, Ling M;Simon, Tony J
通讯作者：
Simon, Tony J
DOI：
10.4088/jcp.08m04476
发表时间：
2009-06
期刊：
The Journal of clinical psychiatry
影响因子：
--
作者：
Bourgeois JA;Coffey SM;Rivera SM;Hessl D;Gane LW;Tassone F;Greco C;Finucane B;Nelson L;Berry-Kravis E;Grigsby J;Hagerman PJ;Hagerman RJ
通讯作者：
Hagerman RJ
DOI：
10.2310/jim.0b013e3181af59d6
发表时间：
2009-12
期刊：
Journal of investigative medicine : the official publication of the American Federation for Clinical Research
影响因子：
--
作者：
Berman RF;Willemsen R
通讯作者：
Willemsen R