Normal social seeking behavior, hypoactivity and reduced exploratory range in a mouse model of Angelman syndrome
Normal social seeking behavior, hypoactivity and reduced exploratory range in a mouse model of Angelman syndrome
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DOI：
10.1186/1471-2156-12-7
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发表时间：
2011-01-14
期刊：
影响因子：
2.9
通讯作者：
Heck, Detlef H.
中科院分区：
文献类型：
--
作者：
Allensworth, Melody;Saha, Anand;Heck, Detlef H.
背景：Angelman综合征(AS)是一种神经遗传性疾病，以严重发育迟缓伴精神发育迟缓、性格开朗、共济失调和特征行为如不恰当的笑声、社交寻求行为和多动等为特征。大多数强直性脊柱炎病例是由于UBE3A基因母体拷贝丢失所致。母体Ube3a缺乏症(Ube3a(m-/p+))和Ube3a表达完全缺失(Ube3a(m-/p-))已在本实验所用小鼠模型中复制。结果：在Ube3a缺陷性AS小鼠模型中是否复制了两种表型特征--社交寻求行为和多动。我们将社交寻求行为量化为与陌生人老鼠近距离接触的时间，并将活动量化为探索过程中移动所用的总时间、移动速度和探索路径的总长度。所有三种基因(Ube3a(m+/p+)、Ube3a(m-/p+)、Ube3a(m-/p-))的小鼠在与陌生人的亲密接触中花费了相同的时间，这表明小鼠缺乏Ube3a并不会导致社交寻求行为的增加或社交去抑制。与野生型相比，Ube3a基因缺陷小鼠的活动水平显著降低，运动速度更慢，探索路径更短，探索范围更小。结论：尽管多动和社交寻求行为是人类Angelman综合征的特征表型，但与野生型小鼠相比，Ube3a基因缺陷小鼠模型不能复制这些表型。这些表型差异可以用遗传缺陷大小的差异来解释，因为患者有70%的缺失，包括UBE3A基因座周围的其他几个基因。
Background: Angelman syndrome (AS) is a neurogenetic disorder characterized by severe developmental delay with mental retardation, a generally happy disposition, ataxia and characteristic behaviors such as inappropriate laughter, social-seeking behavior and hyperactivity. The majority of AS cases are due to loss of the maternal copy of the UBE3A gene. Maternal Ube3a deficiency (Ube3a(m-/p+)), as well as complete loss of Ube3a expression (Ube3a(m-/p-)), have been reproduced in the mouse model used here.Results: Here we asked if two characteristic AS phenotypes - social-seeking behavior and hyperactivity - are reproduced in the Ube3a deficient mouse model of AS. We quantified social-seeking behavior as time spent in close proximity to a stranger mouse and activity as total time spent moving during exploration, movement speed and total length of the exploratory path. Mice of all three genotypes (Ube3a(m+/p+), Ube3a(m-/p+), Ube3a(m-/p-)) were tested and found to spend the same amount of time in close proximity to the stranger, indicating that Ube3a deficiency in mice does not result in increased social seeking behavior or social dis-inhibition. Also, Ube3a deficient mice were hypoactive compared to their wild-type littermates as shown by significantly lower levels of activity, slower movement velocities, shorter exploratory paths and a reduced exploratory range.Conclusions: Although hyperactivity and social-seeking behavior are characteristic phenotypes of Angelman Syndrome in humans, the Ube3a deficient mouse model does not reproduce these phenotypes in comparison to their wild-type littermates. These phenotypic differences may be explained by differences in the size of the genetic defect as similar to 70% of AS patients have a deletion that includes several other genes surrounding the UBE3A locus.