Are Sema5a mutant mice a good model of autism? A behavioral analysis of sensory systems, emotionality and cognition.

Are Sema5a mutant mice a good model of autism? A behavioral analysis of sensory systems, emotionality and cognition.
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DOI:
10.1016/j.bbr.2011.07.008
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发表时间:
2011-11-20
影响因子:
2.7
通讯作者:
Brown, Richard E.
Brown, Richard E.
中科院分区:
心理学3区
文献类型:
--
作者:
Gunn, Rhian K.;Huentelman, Matthew J.;Brown, Richard E.

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Semaphorin 5A(Sema 5A)在自闭症患者的大脑中表达减少,因此Sema 5A水平降低的小鼠可以作为这种神经发育障碍的模型。我们测试了雄性和雌性Sema 5a基因敲除小鼠(B6.129P2SEMA5A<TM1DGEN>/J)和C57 BL/6 J对照的情绪性、视觉能力、前脉冲抑制、运动学习和认知。总的来说,在情绪上只有两个基因型差异:Sema 5a突变小鼠在高架十字迷宫中有更多的伸展-照顾姿势,在开放场地有更多的排便。所有小鼠都能看到,但Sema 5a小鼠的视觉能力比C57 BL/6 J小鼠更好。在感觉-运动门控方面没有基因型差异。Sema 5a小鼠在高架十字迷宫和亮/暗过渡箱中表现出更高水平的活动,并且在Rotarod中存在性别基因型差异,表明受Sema 5a差异影响的平衡和协调的性别差异。没有基因型对认知的影响:Sema 5a小鼠在Morris水迷宫,设置转换或线索和上下文恐惧条件反射中与C57 BL/6 J没有差异。在社会认知测试中,所有小鼠都偏好社会刺激,但对社会新奇性没有偏好,因此Sema 5A小鼠在社会行为方面没有缺陷。总的来说,有一些性别差异,女性表现出更大的活动和男性表现更好的空间学习和记忆的测试,但没有缺陷的Sema 5A小鼠的行为。我们的结论是,Sema 5a小鼠不符合自闭症小鼠模型的行为标准。
Semaphorin 5A (Sema5A) expression is reduced in the brain of individuals with autism, thus mice with reduced Sema5A levels may serve as a model of this neurodevelopmental disorder. We tested male and female Sema5a knockout mice (B6.129P2SEMA5A<TM1DGEN>/J) and C57BL/6J controls for emotionality, visual ability, prepulse inhibition, motor learning and cognition. Overall, there were only two genotype differences in emotionality: Sema5a mutant mice had more stretch-attend postures in the elevated plus-maze and more defecations in the open field. All mice could see, but Sema5a mice had better visual ability than C57BL/6J mice. There were no genotype differences in sensory-motor gating. Sema5a mice showed higher levels of activity in the elevated plus-maze and light/dark transition box, and there were sex by genotype differences in the Rotarod, suggesting a sex difference in balance and coordination differentially affected by Sema5a. There were no genotype effects on cognition: Sema5a mice did not differ from C57BL/6J in the Morris water maze, set-shifting or cued and contextual fear conditioning. In the social recognition test, all mice preferred social stimuli, but there was no preference for social novelty, thus the Sema5A mice do not have a deficit in social behavior. Overall, there were a number of sex differences, with females showing greater activity and males performing better in tests of spatial learning and memory, but no deficits in the behavior of Sema5A mice. We conclude that the Sema5a mice do not meet the behavioral criteria for a mouse model of autism.
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