Ahmed Z, Archer J R, Brown R A
Plastic Surgery, Tissue Repair Unit, University College London Medical School, 1st Floor Charles Bell House, 67-73 Riding House Street, London WIP 7LD, UK.
Calcif Tissue Int. 1997 Jun;60(6):561-6. doi: 10.1007/s002239900280.
The tich mutation leads to the abnormal development of bones in mice such that a 'V-shaped' tongue of noncalcified cartilage appears in the central portion of the proximal tibial growth plate. In this study, alcian green staining of cartilage glycosaminoglycans was used to demonstrate the pattern of limb development in embryos of stage-matched tich and normal, co-isogenic, A.TL mice from the earliest stages in skeletogenesis. The growth plates of normal A.TL siblings were symmetrical across the limb rudiment whereas the growth plate in tich siblings show the beginnings of a V-shaped tongue of cartilage reaching towards the diaphysis. This showed first at E16.5. It was apparent that the crown rump distance, tibia, ulna, and the length of calcified cartilage in tich were significantly shorter than A.TL. These results confirmed that calcification was not the primary defect in tich but point to a temporal dysfunction in growth factor expression (possibly bone morphogenetic proteins) that stems from early limb bud formation and translates through later stages in development.
tich突变导致小鼠骨骼发育异常，使得在近端胫骨生长板的中央部分出现一个“V形”的未钙化软骨舌。在本研究中，利用软骨糖胺聚糖的阿尔新蓝染色来展示与tich品系阶段匹配的正常同基因A.TL小鼠胚胎从骨骼发生最早阶段开始的肢体发育模式。正常A.TL同胞的生长板在肢体原基上是对称的，而tich同胞的生长板则显示出一个向骨干延伸的V形软骨舌的雏形。这最早在胚胎发育第16.5天出现。很明显，tich小鼠的顶臀距、胫骨、尺骨以及钙化软骨长度均显著短于A.TL小鼠。这些结果证实，钙化并非tich小鼠的主要缺陷，而是表明生长因子表达（可能是骨形态发生蛋白）存在暂时性功能障碍，这种障碍源于早期肢芽形成，并贯穿发育后期。
