Department of Psychology/Behavioral Neuroscience, University of Connecticut, Storrs, Connecticut, United States of America.
PLoS One. 2013 Sep 9;8(9):e73144. doi: 10.1371/journal.pone.0073144. eCollection 2013.
Disruption of neuronal migration in humans is associated with a wide range of behavioral and cognitive outcomes including severe intellectual disability, language impairment, and social dysfunction. Furthermore, malformations of cortical development have been observed in a number of neurodevelopmental disorders (e.g. autism and dyslexia), where boys are much more commonly diagnosed than girls (estimates around 4 to 1). The use of rodent models provides an excellent means to examine how sex may modulate behavioral outcomes in the presence of comparable abnormal neuroanatomical presentations. Initially characterized by Rosen et al. 2012, the BXD29- Tlr4(lps-2J) /J mouse mutant exhibits a highly penetrant neuroanatomical phenotype that consists of bilateral midline subcortical nodular heterotopia with partial callosal agenesis. In the current study, we confirm our initial findings of a severe impairment in rapid auditory processing in affected male mice. We also report that BXD29- Tlr4(lps-2J) /J (mutant) female mice show no sparing of rapid auditory processing, and in fact show deficits similar to mutant males. Interestingly, female BXD29- Tlr4(lps-2J) /J mice do display superiority in Morris water maze performance as compared to wild type females, an affect not seen in mutant males. Finally, we report new evidence that BXD29- Tlr4(lps-2J) /J mice, in general, show evidence of hyper-social behaviors. In closing, the use of the BXD29- Tlr4(lps-2J) /J strain of mice - with its strong behavioral and neuroanatomical phenotype - may be highly useful in characterizing sex independent versus dependent mechanisms that interact with neural reorganization, as well as clinically relevant abnormal behavior resulting from aberrant neuronal migration.
人类神经元迁移的破坏与广泛的行为和认知结果有关，包括严重的智力障碍、语言障碍和社交功能障碍。此外，皮质发育畸形已在许多神经发育障碍中观察到（例如自闭症和诵读困难），男孩的诊断率明显高于女孩（估计约为 4 比 1）。使用啮齿动物模型提供了一种极好的方法来研究在存在类似异常神经解剖学表现的情况下，性别如何调节行为结果。最初由 Rosen 等人描述。2012 年，BXD29-Tlr4(lps-2J)/J 突变小鼠表现出高度穿透性的神经解剖表型，包括双侧中线皮质下结节性异位和部分胼胝体发育不全。在本研究中，我们证实了我们最初发现的受影响雄性小鼠快速听觉处理严重受损的发现。我们还报告说，BXD29-Tlr4(lps-2J)/J（突变）雌性小鼠没有快速听觉处理的保留，实际上表现出与突变雄性相似的缺陷。有趣的是，与野生型雌性相比，雌性 BXD29-Tlr4(lps-2J)/J 小鼠在 Morris 水迷宫性能上表现出优势，而突变雄性则没有这种情况。最后，我们报告了新的证据，即 BXD29-Tlr4(lps-2J)/J 小鼠通常表现出过度社交行为的迹象。总之，BXD29-Tlr4(lps-2J)/J 小鼠的使用——具有强烈的行为和神经解剖表型——可能非常有助于描述与神经重组相互作用的性别独立和依赖机制，以及由异常神经元迁移引起的临床相关异常行为。
