Paternal Aging Affects Behavior in Pax6 Mutant Mice: A Gene/Environment Interaction in Understanding Neurodevelopmental Disorders.
Paternal Aging Affects Behavior in Pax6 Mutant Mice: A Gene/Environment Interaction in Understanding Neurodevelopmental Disorders.
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DOI：
10.1371/journal.pone.0166665
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Osumi N
中科院分区：
文献类型：
--
作者：
Yoshizaki K;Furuse T;Kimura R;Tucci V;Kaneda H;Wakana S;Osumi N
神经发育障碍，如自闭症谱系障碍（ASD）和注意力缺陷多动障碍（ADHD）在过去几十年中有所增加。这些神经发育障碍的特征在于复杂的病因学，其涉及多个基因和基因-环境相互作用。控制神经发育特定特性的各种基因在与神经发育障碍相关的表型的发生和严重程度中发挥关键作用。此外，据报道，父亲衰老是导致ASD和ADHD风险的因素之一。在这里，我们报告，为第一次，父亲的衰老有深远的影响，对行为异常的小鼠携带突变的Pax 6，一个基因与神经发育调节功能的发病。我们采用体外受精方法来限制其他因素的影响。在Sey/+小鼠（即，Pax 6突变杂合子），其来自年轻或年老的Sey/+父亲的精子的体外受精。在四个组中未发现体重变化，即，Sey/+和野生型（WT）小鼠出生于年轻或年老的父亲。然而，我们发现重要的差异，母亲分离诱导的超声波发声的Sey/+小鼠出生的年轻父亲和Sey/+小鼠出生的多动的水平，从老年父亲在旷场试验中，分别与WT同窝出生。与年轻父亲所生相比，老年父亲所生的两种基因型的焦虑表型。四组之间在社会行为和感觉运动门控方面差异无统计学意义。这些结果表明，具有单一遗传风险因素的小鼠可以根据父系年龄发展不同的表型。我们的研究主张认真考虑父系衰老在动物研究育种策略中的作用。
Neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit and hyperactivity disorder (ADHD) have increased over the last few decades. These neurodevelopmental disorders are characterized by a complex etiology, which involves multiple genes and gene-environmental interactions. Various genes that control specific properties of neural development exert pivotal roles in the occurrence and severity of phenotypes associated with neurodevelopmental disorders. Moreover, paternal aging has been reported as one of the factors that contribute to the risk of ASD and ADHD. Here we report, for the first time, that paternal aging has profound effects on the onset of behavioral abnormalities in mice carrying a mutation of Pax6, a gene with neurodevelopmental regulatory functions. We adopted an in vitro fertilization approach to restrict the influence of additional factors. Comprehensive behavioral analyses were performed in Sey/+ mice (i.e., Pax6 mutant heterozygotes) born from in vitro fertilization of sperm taken from young or aged Sey/+ fathers. No body weight changes were found in the four groups, i.e., Sey/+ and wild type (WT) mice born to young or aged father. However, we found important differences in maternal separation-induced ultrasonic vocalizations of Sey/+ mice born from young father and in the level of hyperactivity of Sey/+ mice born from aged fathers in the open-field test, respectively, compared to WT littermates. Phenotypes of anxiety were observed in both genotypes born from aged fathers compared with those born from young fathers. No significant difference was found in social behavior and sensorimotor gating among the four groups. These results indicate that mice with a single genetic risk factor can develop different phenotypes depending on the paternal age. Our study advocates for serious considerations on the role of paternal aging in breeding strategies for animal studies.
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影响因子：
5.3
作者：
Franke B;Neale BM;Faraone SV
通讯作者：
Faraone SV
DOI：
10.1002/ajmg.b.31246
发表时间：
2011-12-01
影响因子：
2.8
作者：
Hinney, Anke;Scherag, Andre;Hebebrand, Johannes
通讯作者：
Hebebrand, Johannes
影响因子：
6.9
作者：
BAILEY, A;LECOUTEUR, A;RUTTER, M
通讯作者：
RUTTER, M
影响因子：
5.3
作者：
Davis, L. K.;Meyer, K. J.;Wassink, T. H.
通讯作者：
Wassink, T. H.
影响因子：
11.4
作者：
Chao, Ying-Chi;Chen, Chih-Cheng;Yang, Ruey-Bing
通讯作者：
Yang, Ruey-Bing