DZNE, German Center for Neurodegenerative Diseases, Bonn, Germany.
Mol Psychiatry. 2012 Jan;17(1):62-70. doi: 10.1038/mp.2010.115. Epub 2010 Nov 16.
Approximately 40-50% of individuals affected by tuberous sclerosis (TSC) develop autism spectrum disorders (ASDs). One possible explanation for this partial penetrance is an interaction between TSC gene mutations and other risk factors such as gestational immune activation. In this study, we report the interactive effects of these two ASD risk factors in a mouse model of TSC. Combined, but not single, exposure had adverse effects on intrauterine survival. Additionally, provisional results suggest that these factors synergize to disrupt social approach behavior in adult mice. Moreover, studies in human populations are consistent with an interaction between high seasonal flu activity in late gestation and TSC mutations in ASD. Taken together, our studies raise the possibility of a gene × environment interaction between heterozygous TSC gene mutations and gestational immune activation in the pathogenesis of TSC-related ASD.
约 40-50%的结节性硬化症（TSC）患者会发展出自闭症谱系障碍（ASD）。这种部分外显率的一个可能解释是 TSC 基因突变与其他风险因素（如妊娠期免疫激活）之间的相互作用。在这项研究中，我们报告了 TSC 小鼠模型中这两个 ASD 风险因素的相互作用。联合而非单一暴露对宫内生存有不良影响。此外，初步结果表明，这些因素协同作用破坏成年小鼠的社交趋近行为。此外，人群研究与妊娠期晚期高季节性流感活动和 ASD 中的 TSC 突变之间存在相互作用一致。总之，我们的研究提出了杂合 TSC 基因突变和妊娠期免疫激活之间在 TSC 相关 ASD 发病机制中存在基因×环境相互作用的可能性。
