Prenatal ontogeny of the dopamine-dependent neurobehavioral phenotype in Pitx3-deficient mice.
Prenatal ontogeny of the dopamine-dependent neurobehavioral phenotype in Pitx3-deficient mice.
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Pitx3 缺陷小鼠多巴胺依赖性神经行为表型的产前个体发育。
DOI：
10.1111/ejn.12184
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Ronca,AprilE
中科院分区：
文献类型：
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作者：
Kleven,GaleA;Joshi,Priyanka;Voogd,Marco;Ronca,AprilE
具有出生前多巴胺能功能改变的小鼠模型可以为识别胎儿行为异常和依赖多巴胺的潜在神经底物提供新的机会。在这项研究中，我们验证了一种假设，即产前黑质纹状体功能的丧失与胎儿运动迟缓或启动运动困难有关。对孕期为Pitx3ak/2J和C57BL/6J的母羊后代在出生前最后4天(妊娠19天的E15-18)的特定行为进行了分析。我们使用数字摄像技术分析了：(I)行为状态，通过量化高幅度和低幅度的运动，(Ii)肢体间运动同步性，衡量肢体对自发运动之间的时间关系，(Iii)面部擦拭，这是一种对口周触觉刺激的特征反应，类似于人类婴儿的防御反应，以及(Iv)口腔抓住非营养性乳头，这是人类婴儿哺乳的组成部分。Pitx3突变体在最短的时间间隔(S 0.1%)显示出肢体间运动同步率的选择性降低，同时显着增加了表现出面部擦拭和口腔抓握的潜伏期。总而言之，我们的发现提供了证据，证明了Pitx3突变的主要胎儿神经行为缺陷是与黑质纹状体损伤相关的运动障碍。其他特别令人感兴趣的发现是C57BL/6J和Pitx3杂合子受试者在神经行为功能上的差异，这表明这两组人不是同等的对照组。这些结果进一步表明，胎儿神经行为评估是新出现的神经功能障碍的敏感指标，可能对产前诊断有用。
Mouse models with prenatal alterations in dopaminergic functioning can provide new opportunities to identify fetal behavioral abnormalities and the underlying neural substrates dependent on dopamine. In this study, we tested the hypothesis that prenatal loss of nigrostriatal function is associated with fetal akinesia, or difficulty initiating movement. Specific behaviors were analysed in fetal offspring derived from pregnant Pitx3ak/2J and C57BL/6J dams on the last 4 days before birth (E15‐18 of a 19‐day gestation). Using digital videography, we analysed: (i) behavioral state, by quantification of high‐ and low‐amplitude movements, (ii) interlimb movement synchrony, a measure of the temporal relationship between spontaneous movements of limb pairs, (iii) facial wiping, a characteristic response to perioral tactile stimulation similar to the defensive response in human infants, and (iv) oral grasp of a non‐nutritive nipple, a component of suckling in the human infant. Pitx3 mutants showed a selective decrease in interlimb movement synchrony rates at the shortest (0.1 s) temporal interval coupled with significantly increased latencies to exhibit facial wiping and oral grasp. Collectively, our findings provide evidence that the primary fetal neurobehavioral deficit of the Pitx3 mutation is akinesia related to nigrostriatal damage. Other findings of particular interest were the differences in neurobehavioral functioning between C57BL/6J and Pitx3 heterozygous subjects, suggesting the two groups are not equivalent controls. These results further suggest that fetal neurobehavioral assessments are sensitive indicators of emerging neural dysfunction, and may have utility for prenatal diagnosis.