唐氏综合征小鼠模型中的发育异常与年龄相关的神经退行性变
Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome.
作者信息
Holtzman D M, Santucci D, Kilbridge J, Chua-Couzens J, Fontana D J, Daniels S E, Johnson R M, Chen K, Sun Y, Carlson E, Alleva E, Epstein C J, Mobley W C
机构信息
Department of Neurology, Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110, USA.
出版信息
Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13333-8. doi: 10.1073/pnas.93.23.13333.
Abstract
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.
摘要
为研究唐氏综合征（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——16号染色体部分三体（Ts65Dn）小鼠。Ts65Dn小鼠有小鼠16号染色体远端的额外拷贝，该片段与人21号染色体同源，包含许多导致DS表型的遗传物质。Ts65Dn小鼠在出生后表现出发育延迟，幼年和成年动物均有异常行为，可能类似于智力迟钝。尽管Ts65Dn小鼠的大脑大体检查正常，但存在与年龄相关的隔海马胆碱能神经元变性和星形细胞肥大，这是老年DS个体中出现的阿尔茨海默病病理学特征。这些发现表明，Ts65Dn小鼠可用于研究DS大脑中的某些发育和退行性异常。
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