Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome
Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome
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DOI：
10.1073/pnas.93.23.13333
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发表时间：
1996-11-12
影响因子：
11.1
通讯作者：
Mobley, WC
中科院分区：
文献类型：
--
作者：
Holtzman, DM;Santucci, D;Mobley, WC
为了研究唐氏综合征(DS)中枢神经系统异常的发病机制，我们分析了一种新的DS遗传模型--部分三体16(Ts65Dn)小鼠。Ts65Dn小鼠拥有小鼠16号染色体远端的额外副本，这是一段与人类21号染色体同源的片段，包含了导致DS表型的大部分遗传物质。Ts65Dn小鼠在出生后表现出发育迟缓，幼年和成年动物的异常行为可能类似于智力低下。虽然Ts65Dn的大体检查是正常的，但有与年龄相关的隔海马胆碱能神经元退化和星形细胞肥大，这是老年痴呆症患者存在的阿尔茨海默病病理的标志。这些发现表明，Ts65Dn小鼠可能被用来研究DS脑中的某些发育和退行性异常。
To study the pathogenesis of central nervous system abnormalities in Down syndrome (DS), we have analyzed a new genetic model of DS, the partial trisomy 16 (Ts65Dn) mouse. Ts65Dn mice have an extra copy of the distal aspect of mouse chromosome 16, a segment homologous to human chromosome 21 that contains much of the genetic material responsible for the DS phenotype. Ts65Dn mice show developmental delay during the postnatal period as well as abnormal behaviors in both young and adult animals that may be analogous to mental retardation. Though the Ts65Dn brain is normal on gross examination, there is age-related degeneration of septohippocampal cholinergic neurons and astrocytic hypertrophy, markers of the Alzheimer disease pathology that is present in elderly DS individuals. These findings suggest that Ts65Dn mice may be used to study certain developmental and degenerative abnormalities in the DS brain.