Analysis for a transgenic mouse with facial malformations.

此前，为了构建家族性淀粉样多发性神经病的小鼠模型，已经通过诱导人类突变的反式甲状腺激素基因产生了一系列转基因小鼠。这只老鼠显示了面部发育的一种常染色体突变。面部畸形的特征是鼻子短，上颌扭曲。为了分析面部发育异常的原发事件，对该突变小鼠在妊娠11.5天、13.5天、15.5天和17.5天(Plug d=0)的胚胎进行了形态观察，在11.5天的胚胎中，面部原基形成时，没有观察到面部异常。在13.5天及以后的胚胎中，解剖和光镜下观察到面部异常。与正常胚胎相比，异常胚胎略小，表现为口鼻较短，上唇中央有深裂缝。光镜观察发现，在15.5天和17.5天的胚胎中，面部的一些骨骼和肌肉发育不良。根据这些结果，在13.5天的胚胎中首次检测到的面部异常被证明与成年转基因小鼠的面部异常相似。提示面骨的短吻和异常骨化与颅神经嵴细胞的异常行为有关。断奶后，上颌扭曲引起的咬合异常可能是通过咀嚼对弱骨和肌肉组织的继发性诱导。

A line of transgenic mice has previously been produced by inducing the human mutant transthyretin gene in an effort to construct a mouse model of familial amyloid polyneuropathy. This mouse shows an autosomal mutation of facial development. The facial malformation was characterized by a short snout and a twisted upper jaw. In order to analyze the primary event of the abnormal facial development, embryos of this mutant mouse were observed morphologically on 11.5, 13.5, 15.5 and 17.5 days of gestation(plug day = 0).In the 11.5-day embryos, when the facial primordia were formed, facial abnormalities were not observed. In embryos of 13.5-day and afterwards, facial abnormalities were observed at dissection and light microscopic levels. Abnormal embryos were a little small compared to normal ones and showed -the short snout and also the deep fissure in the center of the upper lip. Light microscopic observations revealed that some of the facial bones and muscles were hypoplastic in embryos of 15.5 and 17.5-day. From these results, the facial abnormalities in embryos firstly detected on 13.5-day were proved to be similar to those in an adult transgenic mice. It is suggested that the short snout and abnormal ossification of facial bones are related to abnormal behavior of cranial neural crest cells. Abnormal occlusion caused by the twisted upper jaw is assumed to be secondarily induced on the weak bone and muscle tissues by mastication after weaning.