Schneider Jürgen E, Bamforth Simon D, Farthing Cassandra R, Clarke Kieran, Neubauer Stefan, Bhattacharya Shoumo
Department of Cardiovascular Medicine, University of Oxford, British Heart Foundation Molecular Cardiology Laboratory, Wellcome Trust Centre for Human Genetics, Oxford, UK.
J Anat. 2003 Feb;202(2):239-47. doi: 10.1046/j.1469-7580.2003.00157.x.
An efficient investigation of the effects of genetic or environmental manipulation on mouse development relies on the rapid and accurate screening of a substantial number of embryos for congenital malformations. Here we demonstrate that it is possible to examine normal organ development and identify malformations in mouse embryos by magnetic resonance microscopy in a substantially shorter time than by conventional histology. We imaged embryos in overnight runs of under 9 h, with an operator time of less than 1 h. In normal embryos we visualized the brain, spinal cord, ganglia, eyes, inner ear, pituitary, thyroid, thymus, trachea, bronchi, lungs, heart, kidneys, gonads, adrenals, oesophagus, stomach, intestines, spleen, liver and pancreas. Examination of the brain in embryos lacking the transcriptional coactivator Cited2 showed cerebellar and midbrain roof agenesis, in addition to exencephaly. In these embryos we were also able to detect agenesis of the adrenal gland. We confirmed all malformations by histological sectioning. Thus magnetic resonance microscopy can be used to rapidly identify developmental and organ malformations in mutant mouse embryos generated by transgenic techniques, in high-throughput mutagenesis screens, or in screens to identify teratogenic compounds and environmental factors contributing to developmental malformations.
对基因或环境操纵对小鼠发育的影响进行有效研究,依赖于对大量胚胎进行快速、准确的先天性畸形筛查。在此,我们证明,通过磁共振显微镜检查,可以在比传统组织学短得多的时间内检查小鼠胚胎的正常器官发育并识别畸形。我们在不到9小时的夜间扫描中对胚胎进行成像,操作人员时间不到1小时。在正常胚胎中,我们可视化了大脑、脊髓、神经节、眼睛、内耳、垂体、甲状腺、胸腺、气管、支气管、肺、心脏、肾脏、性腺、肾上腺、食道、胃、肠、脾、肝和胰腺。对缺乏转录共激活因子Cited2的胚胎进行大脑检查时,除了无脑畸形外,还显示出小脑和中脑顶部发育不全。在这些胚胎中,我们还能够检测到肾上腺发育不全。我们通过组织切片证实了所有畸形。因此,磁共振显微镜可用于在转基因技术产生的突变小鼠胚胎、高通量诱变筛选或识别致畸化合物和导致发育畸形的环境因素的筛选中,快速识别发育和器官畸形。