Department of Neurology & Neurotherapeutics, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-8813.
Neuroscience Graduate Program, The University of Texas Southwestern Medical Center, Dallas, TX, 75390.
Autism Res. 2018 Feb;11(2):234-244. doi: 10.1002/aur.1857. Epub 2017 Oct 13.
Neuroligin-3 (NLGN3) is a postsynaptic cell adhesion protein that interacts with presynaptic ligands including neurexin-1 (NRXN1) [Ichtchenko et al., Journal of Biological Chemistry, 271, 2676-2682, 1996]. Mice harboring a mutation in the NLGN3 gene (NL3R451C) mimicking a mutation found in two brothers with autism spectrum disorder (ASD) were previously generated and behaviorally phenotyped for autism-related behaviors. In these NL3R451C mice generated and tested on a hybrid C57BL6J/129S2/SvPasCrl background, we observed enhanced spatial memory and reduced social interaction [Tabuchi et al., Science, 318, 71-76, 2007]. Curiously, an independently generated second line of mice harboring the same mutation on a C57BL6J background exhibited minimal aberrant behavior, thereby providing apparently discrepant results. To investigate the origin of the discrepancy, we previously replicated the original findings of Tabuchi et al. by studying the same NL3R451C mutation on a pure 129S2/SvPasCrl genetic background. Here we complete the behavioral characterization of the NL3R451C mutation on a pure C57BL6J genetic background to determine if background genetics play a role in the discrepant behavioral outcomes involving NL3R451C mice. NL3R451C mutant mice on a pure C57BL6J background did not display spatial memory enhancements or social interaction deficits. We only observed a decreased startle response and mildly increased locomotor activity in these mice suggesting that background genetics influences behavioral outcomes involving the NL3R451C mutation. Autism Res 2018, 11: 234-244. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
Behavioral symptoms of autism can be highly variable, even in cases that involve identical genetic mutations. Previous studies in mice with a mutation of the Neuroligin-3 gene showed enhanced learning and social deficits. We replicated these findings on the same and different genetic backgrounds. In this study, however, the same mutation in mice on a different genetic background did not reproduce our previous findings. Our results suggest that genetic background influences behavioral symptoms of this autism-associated mutation.
神经突黏附蛋白 3（NLGN3）是一种突触后细胞黏附蛋白，与突触前配体相互作用，包括神经连接蛋白 1（NRXN1）[Ichtchenko 等人，《生物化学杂志》，271，2676-2682，1996]。先前已经生成并表型分析了携带神经突黏附蛋白 3 基因（NL3R451C）突变的小鼠，该突变模拟了两个自闭症谱系障碍（ASD）兄弟的突变[Tabuchi 等人，《科学》，318，71-76，2007]。在这些基于杂交 C57BL6J/129S2/SvPasCrl 背景生成和测试的 NL3R451C 小鼠中，我们观察到空间记忆增强和社交互动减少[Tabuchi 等人，《科学》，318，71-76，2007]。奇怪的是，在 C57BL6J 背景下携带相同突变的另一个独立生成的第二线小鼠表现出最小的异常行为，从而提供了明显不同的结果。为了研究差异的起源，我们之前通过在纯 129S2/SvPasCrl 遗传背景上研究相同的 NL3R451C 突变，复制了 Tabuchi 等人的原始发现。在这里，我们在纯 C57BL6J 遗传背景上完成了 NL3R451C 突变的行为特征描述，以确定 NL3R451C 小鼠的差异行为结果是否涉及背景遗传学。在纯 C57BL6J 背景下的 NL3R451C 突变小鼠没有表现出空间记忆增强或社交互动缺陷。我们只观察到这些小鼠的惊跳反应降低和运动活性略有增加，这表明背景遗传学影响涉及 NL3R451C 突变的行为结果。自闭症研究 2018，11：234-244。©2017 自闭症国际研究协会，威利期刊，公司。
自闭症的行为症状可能高度可变，即使在涉及相同基因突变的情况下也是如此。先前在具有神经突黏附蛋白 3 基因突变的小鼠中的研究显示出学习和社交缺陷增强。我们在相同和不同的遗传背景上复制了这些发现。然而，在这项研究中，在不同遗传背景下的相同突变小鼠没有再现我们之前的发现。我们的结果表明，遗传背景会影响与这种自闭症相关突变相关的行为症状。
