LEVENE C I, GROSS J
J Exp Med. 1959 Nov 1;110(5):771-90. doi: 10.1084/jem.110.5.771.
The lathyrogenic agents, beta-aminopropionitrile and semicarbizide, when applied to the chorio-allantoic membrane of the chick embryo produced a dramatic increase in fragility of the embryo. This alteration was not associated with a change in the concentration of collagen, except in aorta, but was accompanied by a sharp increase in the amount of collagen extractible in cold 1 M NaCl from skin, bone, and aorta. Increase in fragility and extractible collagen began within 3 hours after introduction of the agent and rose steadily for at least 72 hours. Essentially no collagen could be extracted from tissues of normal chick embryos. Both fragility and amount of extractible collagen were dosage- and time-dependent. It is concluded that the extractible collagen in lathyrism consists of a large proportion of dissolved fibers previously insoluble and formed prior to administration of the agent. The data also suggest that the "lathyritic" collagen in vivo is not in molecular dispersion but in an aggregate or fibrillar form. It is dispersed by cooling. The extracted collagen could be reconstituted to typical striated fibrils in vitro and the molecule appeared to be normal in the gross, with regard to asymmetry ratio and intramolecular helical structure. The evidence at hand suggests that at least one of the defects induced by lathyrogenic agents is an interference with the normal intermolecular cross-linking within the collagen fibril.
致跛行因子β-氨基丙腈和氨基脲作用于鸡胚的绒毛尿囊膜时，会使胚胎的脆弱性显著增加。这种改变与胶原蛋白浓度的变化无关，但主动脉除外，不过皮肤、骨骼和主动脉中可被冷的1M氯化钠提取的胶原蛋白量会急剧增加。引入该因子后3小时内，脆弱性和可提取胶原蛋白开始增加，并至少持续72小时稳定上升。正常鸡胚组织基本上无法提取出胶原蛋白。脆弱性和可提取胶原蛋白的量均与剂量和时间有关。结论是，致跛行病中的可提取胶原蛋白很大一部分由先前不溶且在施用该因子之前就已形成的溶解纤维组成。数据还表明，体内的“致跛行病”胶原蛋白不是分子分散状态，而是聚集或纤维状形式。它通过冷却而分散。提取的胶原蛋白在体外可重新组装成典型的横纹纤维，从总体上看，分子在不对称比率和分子内螺旋结构方面似乎是正常的。现有证据表明，致跛行因子诱导的缺陷中至少有一个是对胶原纤维内正常分子间交联的干扰。
