Evaluation of Pax6 mutant rat as a model for autism.
Evaluation of Pax6 mutant rat as a model for autism.
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DOI：
10.1371/journal.pone.0015500
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发表时间：
2010-12-21
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：
Umeda T;Takashima N;Nakagawa R;Maekawa M;Ikegami S;Yoshikawa T;Kobayashi K;Okanoya K;Inokuchi K;Osumi N
自闭症是一种高度可变的大脑发育障碍，具有很强的遗传基础。Pax6在大脑发育和维护中起着关键作用。它在胚胎和成体神经干细胞中表达，在整个中枢神经系统的星形胶质细胞中表达，在嗅球、杏仁核、丘脑和小脑的神经元中表达，以高度依赖环境的方式发挥作用。我们最近报道了Pax6基因自发突变的Pax6杂合突变（rSey2/+）大鼠显示出脉冲前抑制（PPI）受损。在本研究中，我们进一步研究了rSey2/+大鼠的行为，发现它们在社会交往中表现出异常（更多的攻击和退缩），以及饲养活动和恐惧条件记忆的损害。rSey2+鼠仔超声发声（USV）雄鼠正常，雌鼠异常。此外，氯氮平治疗成功地恢复了感觉运动门控功能的缺陷，但没有恢复恐惧条件记忆。结合我们之前的人类遗传数据和其他文献的结果，rSey2/+大鼠可能具有自闭症的一些表型成分。
Autism is a highly variable brain developmental disorder and has a strong genetic basis. Pax6 is a pivotal player in brain development and maintenance. It is expressed in embryonic and adult neural stem cells, in astrocytes in the entire central nervous system, and in neurons in the olfactory bulb, amygdala, thalamus, and cerebellum, functioning in highly context-dependent manners. We have recently reported that Pax6 heterozygous mutant (rSey2/+) rats with a spontaneous mutation in the Pax6 gene, show impaired prepulse inhibition (PPI). In the present study, we further examined behaviors of rSey2/+ rats and revealed that they exhibited abnormality in social interaction (more aggression and withdrawal) in addition to impairment in rearing activity and in fear-conditioned memory. Ultrasonic vocalization (USV) in rSey2+ rat pups was normal in male but abnormal in female. Moreover, treatment with clozapine successfully recovered the defects in sensorimotor gating function, but not in fear-conditioned memory. Taken together with our prior human genetic data and results in other literatures, rSey2/+ rats likely have some phenotypic components of autism.
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