Waddington John L, Katina Stanislav, O'Tuathaigh Colm M P, Bowman Adrian W
Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin 2, Ireland.
Jiangsu Key Laboratory of Translational Research & Therapy for Neuro-Psychiatric-Disorders and Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123 China.
Curr Behav Neurosci Rep. 2017;4(4):322-330. doi: 10.1007/s40473-017-0136-3. Epub 2017 Nov 9.
In the context of human developmental conditions, we review the conceptualisation of schizophrenia as a neurodevelopmental disorder, the status of craniofacial dysmorphology as a clinically accessible index of brain dysmorphogenesis, the ability of genetically modified mouse models of craniofacial dysmorphology to inform on the underlying dysmorphogenic process and how geometric morphometric techniques in mutant mice can extend quantitative analysis.
Mutant mice with disruption of neuregulin-1, a gene associated meta-analytically with risk for schizophrenia, constitute proof-of-concept studies of murine facial dysmorphology in a manner analogous to clinical studies in schizophrenia. Geometric morphometric techniques informed on the topography of facial dysmorphology and identified asymmetry therein.
Targeted disruption in mice of genes involved in individual components of developmental processes and analysis of resultant facial dysmorphology using geometric morphometrics can inform on mechanisms of dysmorphogenesis at levels of incisiveness not possible in human subjects.
在人类发育状况的背景下，我们回顾了将精神分裂症概念化为神经发育障碍的情况、颅面畸形作为大脑畸形发生的临床可及指标的现状、颅面畸形转基因小鼠模型用于揭示潜在畸形发生过程的能力，以及突变小鼠中的几何形态测量技术如何扩展定量分析。
神经调节蛋白-1基因功能缺失的突变小鼠，该基因经荟萃分析与精神分裂症风险相关，其构成了小鼠面部畸形的概念验证研究，类似于精神分裂症的临床研究。几何形态测量技术揭示了面部畸形的地形并确定了其中的不对称性。
对参与发育过程各个组成部分的基因在小鼠中进行靶向破坏，并使用几何形态测量学分析由此产生的面部畸形，可以在人类受试者无法达到的精确水平上揭示畸形发生的机制。
