Heterozygous L1-deficient mice express an autism-like phenotype
Heterozygous L1-deficient mice express an autism-like phenotype
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DOI：
10.1016/j.bbr.2015.05.040
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发表时间：
2015-10-01
影响因子：
2.7
通讯作者：
Matzel, Louis D.
中科院分区：
文献类型：
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作者：
Sauce, Bruno;Wass, Christopher;Matzel, Louis D.
L1CAM(L1)基因编码一种细胞黏附分子，在发育和成人神经系统中参与几个重要的过程，包括神经元迁移、存活和可塑性。在人类和小鼠中，X染色体连锁基因L1的突变会导致男性严重的神经缺陷。具有一个L1基因功能拷贝的L1杂合子雌性小鼠表现出不同于L1全缺陷和野生型窝鼠的复杂的形态特征。然而，几乎没有关于L1杂合子小鼠和人类行为的信息。在这里，我们调查了L1基因结构性失活的杂合子雌性小鼠的行为。这些小鼠被与野生型产仔母鼠进行比较。动物接受了五种行为测试的评估：五种焦虑/压力/探索测试，四种运动能力测试，两种空间学习测试，三种社交行为测试，以及三种重复行为测试。我们发现，L1杂合子小鼠表现出类似自闭症的表型，包括社交行为减少和过度自我打扮(这种重复行为在自闭症动物模型中也是典型的)。L1杂合子小鼠也表现出对光的敏感度增加，通过不愿进入新环境的明亮区域进行评估。然而，L1杂合子小鼠的焦虑、压力、运动能力和空间学习水平与野生型小鼠相似。这些观察结果提出了一种可能性，即使用已知的触发L1功能的分子可能会在治疗人类自闭症方面变得有价值。(C)由爱思唯尔出版的2015年。
The L1CAM (L1) gene encodes a cell adhesion molecule that contributes to several important processes in the developing and adult nervous system, including neuronal migration, survival, and plasticity. In humans and mice, mutations in the X chromosome-linked gene L1 cause severe neurological defects in males. L1 heterozygous female mice with one functional copy of the L1 gene show complex morphological features that are different from L1 fully-deficient and wild-type littermate mice. However, almost no information is available on the behavior of L1 heterozygous mice and humans. Here, we investigated the behavior of heterozygous female mice in which the L1 gene is constitutively inactivated. These mice were compared to wild-type littermate females. Animals were assessed in five categories of behavioral tests: five tests for anxiety/stress/exploration, four tests for motor abilities, two tests for spatial learning, three tests for social behavior, and three tests for repetitive behavior. We found that L1 heterozygous mice express an autism-like phenotype, comprised of reduced social behaviors and excessive self-grooming (a repetitive behavior also typical in animal models of autism). L1 heterozygous mice also exhibited an increase in sensitivity to light, assessed by a reluctance to enter the lighted areas of novel environments. However, levels of anxiety, stress, motor abilities, and spatial learning in L1 heterozygous mice were similar to those of wild-type mice. These observations raise the possibility that using molecules known to trigger L1 functions may become valuable in the treatment of autism in humans. (C) 2015 Published by Elsevier B.V.