Disruption of bone development and homeostasis by trisomy in Ts65Dn Down syndrome mice
Disruption of bone development and homeostasis by trisomy in Ts65Dn Down syndrome mice
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DOI：
10.1016/j.bone.2010.09.028
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发表时间：
2011-02-01
期刊：
影响因子：
4.1
通讯作者：
Li, Jiliang
中科院分区：
文献类型：
--
作者：
Blazek, Joshua D.;Gaddy, Anna;Li, Jiliang
唐氏综合征（DS）是一种由21三体引起的遗传性疾病，可导致认知障碍、低肌张力和颅面改变。对DS患者的颅面和无骨骨骼的形态测量研究表明，骨骼发育和体内平衡受到三体的影响。Ts65Dn小鼠模型具有在人类21号染色体上发现的大约一半基因的三个拷贝，并且表现出与在患有DS的人类中观察到的相似的颅面骨骼和大小差异。我们假设Ts65Dn和整倍体小鼠在骨发育和稳态方面存在明显差异，影响颅面和无骨骨骼表型。对6周龄和16周龄的Ts65Dn和对照小鼠股骨的结构和力学性能进行定量评估，发现三体骨的小梁和皮质骨结构、骨矿物质密度、骨形成和骨强度存在显著缺陷。此外，骨矿物质密度和动态牙本质形成率的头骨和门牙，分别，也减少了Ts65 Dn小鼠，表明三体显着影响颅面和approximular骨骼。(C)2010年爱思唯尔公司All rights reserved.
Down syndrome (DS) is a genetic disorder resulting from trisomy 21 that causes cognitive impairment, low muscle tone and craniofacial alterations. Morphometric studies of the craniofacial and appendicular skeleton in individuals with DS suggest that bone development and homeostasis are affected by trisomy. The Ts65Dn mouse model has three copies of approximately half the genes found on human chromosome 21 and exhibits craniofacial skeletal and size differences similar to those observed in humans with DS. We hypothesized that Ts65Dn and euploid mice have distinct differences in bone development and homeostasis influencing both the craniofacial and appendicular skeletal phenotypes. Quantitative assessment of structural and mechanical properties of the femur in Ts65Dn and control mice at 6 and 16 weeks of age revealed significant deficiencies in trabecular and cortical bone architecture, bone mineral density, bone formation, and bone strength in trisomic bone. Furthermore, bone mineral density and dynamic dentin formation rate of the skull and incisor, respectively, were also reduced in Ts65Dn mice, demonstrating that trisomy significantly affects both the craniofacial and appendicular skeleton. (C) 2010 Elsevier Inc. All rights reserved.