Chang H H, Schwartz Z, Kaufman M H
Department of Anatomy, University Medical School, Edinburgh, UK.
J Anat. 1996 Aug;189 ( Pt 1)(Pt 1):37-49.
A mouse model for studying the teratogenic effects of amniotic sac puncture has recently been established (MacIntyre et al. 1995), and the anomalies encountered included cleft palate, limb and tail abnormalities, and postural deformities. In order to investigate the underlying mechanism(s) involved, mouse embryos subjected to amniotic sac puncture on day 13 of gestation were examined externally on day 19, then 'cleared' and bulk stained with alizarin red S and Alcian blue to reveal, respectively, their bony and cartilaginous elements. This procedure allowed a comparison to be made between the incidence of soft tissue anomalies of the distal parts of the limbs and the appearance of the underlying skeletal elements. Despite a high incidence of soft tissue (principally digital) anomalies, relatively few skeletal anomalies were encountered. Measurements of intact long bones, and regions of ossification, were made in the major long bones of 'nonexperimental' and 'internal' controls and 'experimental' fetuses that displayed external morphological malformations to establish whether the experimental procedure had a greater effect on the proximal or distal components of the limb skeleton. No significant difference was observed when the ratios of proximal: distal length were compared with those obtained from the control series. The degree of severity of 'clubhand' and 'clubfoot' deformity was determined, and a comparison made between the severity observed on the right and left sides. This analysis revealed that for 'clubhand', the left forelimb was more severely affected than the right forelimb. The incidence of 'clubfoot' deformity was similar between the 2 sides. A possible explanation for this asymmetric effect is provided. An unexpected finding was the abnormal pattern of ossification seen in the sternum of two thirds of the 'experimental' fetuses that displayed external morphological malformations. This abnormal pattern was seen in none of the controls nor in fetuses in the 'experimental' series that displayed no external morphological malformations.
最近建立了一种用于研究羊膜腔穿刺致畸作用的小鼠模型（MacIntyre等人，1995年），所遇到的异常情况包括腭裂、肢体和尾巴异常以及姿势畸形。为了研究其中涉及的潜在机制，在妊娠第13天接受羊膜腔穿刺的小鼠胚胎在第19天进行外部检查，然后“透明化”并用茜素红S和阿尔辛蓝进行整体染色，分别显示其骨骼和软骨成分。该程序使得能够对肢体远端软组织异常的发生率与潜在骨骼成分的外观进行比较。尽管软组织（主要是指部）异常的发生率很高，但遇到的骨骼异常相对较少。对“非实验性”和“内部”对照以及表现出外部形态畸形的“实验性”胎儿的主要长骨中的完整长骨和骨化区域进行测量，以确定实验程序对肢体骨骼的近端或远端成分是否有更大影响。当将近端与远端长度的比率与从对照系列获得的比率进行比较时，未观察到显著差异。确定了“马蹄内翻手”和“马蹄内翻足”畸形的严重程度，并对左右两侧观察到的严重程度进行了比较。该分析表明，对于“马蹄内翻手”，左前肢比右前肢受影响更严重。两侧“马蹄内翻足”畸形的发生率相似。提供了这种不对称效应的一种可能解释。一个意外发现是，在表现出外部形态畸形的三分之二“实验性”胎儿的胸骨中看到了异常的骨化模式。在对照中以及在没有外部形态畸形的“实验性”系列胎儿中均未看到这种异常模式。
