Analysis for a transgenic mouse with facial malformations.

先前已经通过诱导人突变的甲状腺素运载蛋白基因来产生转基因小鼠品系，以努力构建家族性淀粉样多发性神经病的小鼠模型。这只老鼠显示出面部发育的常染色体突变。面部畸形的特点是短吻和扭曲的上颌。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、13.5、15.5和17.5天（plug day = 0）的胚胎进行形态学观察，在面部原基形成的11.5天胚胎中，未观察到面部异常。在13.5天及以后的胚胎中，在解剖和光学显微镜水平上观察到面部异常。与正常胚胎相比，异常胚胎有点小，并且显示-短吻和上唇中心的深裂。光镜观察发现，在15.5和17.5天的胚胎中，一些面部骨骼和肌肉发育不良。从这些结果中，首次在13.5天的胚胎中检测到的面部异常被证明与成年转基因小鼠中的面部异常相似。提示短吻和面骨异常骨化与颅神经嵴细胞的异常行为有关。上颚扭曲所造成的咬合异常，可能是由断乳后咀嚼所造成的骨骼及肌肉组织的异常。

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.