Enlarged Brain Ventricles and Impaired Neurogenesis in the Ts1Cje and Ts2Cje Mouse Models of Down Syndrome
Enlarged Brain Ventricles and Impaired Neurogenesis in the Ts1Cje and Ts2Cje Mouse Models of Down Syndrome
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DOI：
10.1093/cercor/bhp176
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发表时间：
2010-05-01
期刊：
影响因子：
3.7
通讯作者：
Yamakawa, Kazuhiro
中科院分区：
文献类型：
--
作者：
Ishihara, Keiichi;Amano, Kenji;Yamakawa, Kazuhiro
唐氏综合症(DS)是导致精神发育迟滞的最常见原因。虽然DS患者的脑结构和神经源性异常已显示出来，但其分子病因仍不清楚。为了确定这一点，我们对2只DS小鼠模型Ts1Cje和Ts2Cje的大脑进行了结构和组织学检查。这些小鼠携带不同长度的小鼠16号染色体的三体片段，这些三体片段与人类21号染色体同源。在3月龄时，Ts1Cje和Ts2Cje的脑室扩大程度相似。两只小鼠在侧脑室下区和海马齿状回的双重皮质素阳性神经母细胞和胸腺嘧啶核苷类似物BrdU标记的增殖细胞的数量也出现了类似程度的减少，表明成人神经发生受损。此外，在胚胎第14.5天，两个品系的小鼠与二倍体小鼠相比，大脑较小，皮质神经发生减少，这可能是成年后观察到的脑室扩大的原因。我们的发现表明，Ts1Cje小鼠的三体片段与Ts2Cje小鼠共享，包含导致这些异常表型的基因，并可能与与DS相关的智力低下有关。
Down syndrome (DS) is the most common cause of mental retardation. Although structural and neurogenic abnormalities have been shown in the brains of DS patients, the molecular etiology is still unknown. To define it, we have performed structural and histological examinations of the brains of Ts1Cje and Ts2Cje, 2 mouse models for DS. These mice carry different length of trisomic segments of mouse chromosome 16 that are orthologous to human chromosome 21. At 3 months of age, ventricular enlargements were observed in both Ts1Cje and Ts2Cje brains at a similar degree. Both mice also showed decreases of the number of doublecortin-positive neuroblasts and thymidine-analog BrdU-labeled proliferating cells in the subventricular zone of the lateral ventricles (LVs) and in the hippocampal dentate gyrus at a similar degree, suggesting impaired adult neurogenesis. Additionally, at embryonic day 14.5, both strains of mice, when compared with diploid littermates, had smaller brains and decreased cortical neurogenesis that could possibly contribute to the ventricular enlargements observed in adulthood. Our findings suggest that the trisomic segment of the Ts1Cje mouse, which is shared with Ts2Cje, contains the genes that are responsible for these abnormal phenotypes and could be relevant to the mental retardation associated with DS.