Genetic-background modulation of core and variable autistic-like symptoms in Fmr1 knock-out mice.
Genetic-background modulation of core and variable autistic-like symptoms in Fmr1 knock-out mice.
复制标题
DOI：
10.1371/journal.pone.0017073
复制
发表时间：
2011-02-22
期刊：
影响因子：
3.7
通讯作者：
Crusio WE
中科院分区：
文献类型：
--
作者：
Pietropaolo S;Guilleminot A;Martin B;D'Amato FR;Crusio WE
目前还没有具有良好构建有效性的自闭症谱系障碍（ASD）动物模型;因此，使用以ASD样缺陷为特征但具有已知原因的病理遗传模型可能是一种有希望的策略。Fmr 1-KO小鼠是这种方法的一个例子，它模拟了脆性X综合征，一种众所周知的遗传性疾病，表现为ASD症状。Fmr 1-KO可用于不同的遗传背景（FVB与C57 BL/6），这可能解释了迄今为止这些突变体获得的一些相互矛盾的结果。 在模拟ASD临床症状的一系列测试中检查FVB和C57 BL/6遗传背景的Fmr 1 KO及其野生型同窝仔，包括核心症状三联征（社会互动和交流的改变，重复行为的存在）以及次要症状（感觉运动反应性和昼夜活动模式的紊乱，癫痫事件）。 Fmr 1-KO小鼠表现出类似自闭症的核心症状，即社会互动改变和重复行为的发生，以及额外的多动症。遗传背景调制的Fmr 1缺失的影响，似乎C57 BL/6背景可能更适合于进一步研究核心自闭症样症状。Fmr 1-小鼠系不能概括所有主要的核心和继发性ASD症状，但仍然可以用于阐明特定ASD样内表型的神经生物学机制。
No animal models of autism spectrum disorders (ASD) with good construct validity are currently available; using genetic models of pathologies characterized by ASD-like deficits, but with known causes, may be therefore a promising strategy. The Fmr1-KO mouse is an example of this approach, modeling Fragile X syndrome, a well-known genetic disorder presenting ASD symptoms. The Fmr1-KO is available on different genetic backgrounds (FVB versus C57BL/6), which may explain some of the conflicting results that have been obtained with these mutants up till now. Fmr1 KO and their wild-type littermates on both the FVB and C57BL/6 genetic backgrounds were examined on a battery of tests modeling the clinical symptoms of ASD, including the triad of core symptoms (alterations in social interaction and communication, presence of repetitive behaviors), as well as the secondary symptoms (disturbances in sensori-motor reactivity and in circadian patterns of activity, epileptic events). Fmr1-KO mice displayed autistic-like core symptoms of altered social interaction and occurrence of repetitive behaviors with additional hyperactivity. The genetic background modulated the effects of the Fmr1 deletion and it appears that the C57BL/6 background may be more suitable for further research on core autistic-like symptoms. The Fmr1-mouse line does not recapitulate all of the main core and secondary ASD symptoms, but still can be useful to elucidate the neurobiological mechanisms underlying specific ASD-like endophenotypes.
登录
查看更多内容
影响因子：
1.9
作者：
Brodkin, ES;McDougle, CJ;Price, LH
通讯作者：
Price, LH
影响因子：
2.7
作者：
Csomor, PA;Vollenweider, FX;Yee, BK
通讯作者：
Yee, BK
影响因子：
1.9
作者：
Csomor, Philipp A.;Vollenweider, Franz X.;Quednow, Boris B.
通讯作者：
Quednow, Boris B.
DOI：
10.1073/pnas.141145998
发表时间：
2001-06-19
影响因子：
11.1
作者：
Greenough, WT;Klintsova, AY;Weiler, IJ
通讯作者：
Weiler, IJ
影响因子：
3.5
作者：
Bontekoe, CJM;McIlwain, KL;Oostra, BA
通讯作者：
Oostra, BA