Developmental Neurobiology Unit, Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas & Universidad Miguel Hernández, Sant Joan d'Alacant 03550, Spain.
Cellular and Systems Neurobiology Unit, Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas & Universidad Miguel Hernández, Sant Joan d'Alacant 03550, Spain.
Neuroimage. 2014 Aug 15;97:95-106. doi: 10.1016/j.neuroimage.2014.04.043. Epub 2014 Apr 22.
Genetic mouse models of neurodevelopmental disorders are being massively generated, but technologies for their high-throughput phenotyping are missing. The potential of high-resolution magnetic resonance imaging (MRI) for structural phenotyping has been demonstrated before. However, application to the embryonic mouse central nervous system has been limited by the insufficient anatomical detail. Here we present a method that combines staining of live embryos with a contrast agent together with MR microscopy after fixation, to provide unprecedented anatomical detail at relevant embryonic stages. By using this method we have phenotyped the embryonic forebrain of Robo1/2(-/-) double mutant mice enabling us to identify most of the well-known anatomical defects in these mutants, as well as novel more subtle alterations. We thus demonstrate the potential of this methodology for a fast and reliable screening of subtle structural abnormalities in the developing mouse brain, as those associated to defects in disease-susceptibility genes of neurologic and psychiatric relevance.
神经发育障碍的遗传小鼠模型正在大量生成，但缺乏高通量表型分析技术。高分辨率磁共振成像（MRI）在结构表型分析方面的潜力此前已经得到证实。然而，由于解剖细节不足，其在胚胎鼠中枢神经系统中的应用受到限制。在这里，我们提出了一种将活胚胎染色与造影剂结合，并在固定后进行磁共振显微镜检查的方法，从而在相关胚胎阶段提供前所未有的解剖细节。通过使用这种方法，我们对 Robo1/2(-/-) 双突变体小鼠的胚胎前脑进行了表型分析，使我们能够识别出这些突变体中大多数已知的解剖缺陷，以及新的更微妙的改变。因此，我们证明了该方法在快速可靠地筛选与神经和精神相关疾病易感性基因缺陷相关的发育中鼠脑细微结构异常方面的潜力。
