Abnormalities of cell packing density and dendritic complexity in the MeCP2 A140V mouse model of Rett syndrome/X-linked mental retardation.
Abnormalities of cell packing density and dendritic complexity in the MeCP2 A140V mouse model of Rett syndrome/X-linked mental retardation.
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DOI：
10.1186/1471-2202-11-19
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发表时间：
2010-02-17
期刊：
影响因子：
2.4
通讯作者：
Narayanan V
中科院分区：
文献类型：
--
作者：
Jentarra GM;Olfers SL;Rice SG;Srivastava N;Homanics GE;Blue M;Naidu S;Narayanan V
瑞特综合征（RTT）是女孩智力障碍的常见病因，与MECP2基因的突变有关。大多数女孩的MECP2基因突变病例会导致经典型或变异型的瑞特综合征。当这些相同的突变发生在男性身上时，往往表现为严重的新生儿脑病。然而，一些MECP2突变也可导致以智力障碍综合征为特征的疾病，尤其是在男孩中。其中一种突变A140V是一种常见的、反复出现的错义突变，约占所有MeCP2突变的0.6%，按频率排在第21位。它已在家族性X连锁智力障碍（XLMR）、PPM - X综合征（帕金森症、锥体束征、巨睾症、X连锁智力障碍）以及其他神经精神综合征中被描述。有趣的是，据报道这种突变保留了MeCP2蛋白的甲基 - CpG结合功能，但损害了其与智力障碍相关蛋白ATRX结合的能力。
我们报道了表达A140V MeCP2突变的小鼠模型的构建和初步特征描述。对雄性半合子小鼠的这些初步描述性研究揭示了在瑞特综合征和智力障碍中均可见的脑部异常。发现的异常包括大脑中细胞堆积密度增加以及神经元树突分支的复杂性显著降低。与一些MeCP2突变小鼠模型不同，A140V小鼠具有明显正常的寿命和正常的体重增长模式，没有明显的癫痫发作、震颤、呼吸困难或脊柱后凸。
我们在这个瑞特综合征/X连锁智力障碍小鼠模型中发现了多种神经异常，这可能有助于阐明MECP2突变导致神经元变化从而引起智力障碍的方式，且不受癫痫发作、慢性通气不足或其他瑞特综合征相关症状的干扰。
Rett syndrome (RTT), a common cause of mental retardation in girls, is associated with mutations in the MECP2 gene. Most human cases of MECP2 mutation in girls result in classical or variant forms of RTT. When these same mutations occur in males, they often present as severe neonatal encephalopathy. However, some MECP2 mutations can also lead to diseases characterized as mental retardation syndromes, particularly in boys. One of these mutations, A140V, is a common, recurring missense mutation accounting for about 0.6% of all MeCP2 mutations and ranking 21st by frequency. It has been described in familial X-linked mental retardation (XLMR), PPM- X syndrome (Parkinsonism, Pyramidal signs, Macroorchidism, X-linked mental retardation) and in other neuropsychiatric syndromes. Interestingly, this mutation has been reported to preserve the methyl-CpG binding function of the MeCP2 protein while compromising its ability to bind to the mental retardation associated protein ATRX. We report the construction and initial characterization of a mouse model expressing the A140V MeCP2 mutation. These initial descriptive studies in male hemizygous mice have revealed brain abnormalities seen in both RTT and mental retardation. The abnormalities found include increases in cell packing density in the brain and a significant reduction in the complexity of neuronal dendritic branching. In contrast to some MeCP2 mutation mouse models, the A140V mouse has an apparently normal lifespan and normal weight gain patterns with no obvious seizures, tremors, breathing difficulties or kyphosis. We have identified various neurological abnormalities in this mouse model of Rett syndrome/X-linked mental retardation which may help to elucidate the manner in which MECP2 mutations cause neuronal changes resulting in mental retardation without the confounding effects of seizures, chronic hypoventilation, or other Rett syndrome associated symptoms.
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影响因子：
3.6
作者：
Homanics, GE;Ferguson, C;Firestone, LL
通讯作者：
Firestone, LL
影响因子：
9.9
作者：
Dotti, MT;Orrico, A;Federico, A
通讯作者：
Federico, A
影响因子：
1.7
作者：
BELICHENKO, PV;OLDFORS, A;DAHLSTROM, A
通讯作者：
DAHLSTROM, A
影响因子：
16.2
作者：
Chang, QA;Khare, G;Jaenisch, R
通讯作者：
Jaenisch, R
DOI：
10.1111/j.1651-2227.1985.tb10993.x
发表时间：
1985-01-01
期刊：
ACTA PAEDIATRICA SCANDINAVICA
影响因子：
--
作者：
HAGBERG, B
通讯作者：
HAGBERG, B